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Sample records for dosage dependent suppression

  1. Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

    Science.gov (United States)

    Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

    2010-09-15

    The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

  2. Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development

    Science.gov (United States)

    Peltz, Lindsay; Gomez, Jessica; Marquez, Maribel; Alencastro, Frances; Atashpanjeh, Negar; Quang, Tara; Bach, Thuy; Zhao, Yuanxiang

    2012-01-01

    Studies in the past have illuminated the potential benefit of resveratrol as an anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However, these two different effects were observed at different concentration ranges. Studies of resveratrol in a wide range of concentrations on the same cell type are lacking, which is necessary to comprehend its diverse and sometimes contradictory cellular effects. In this study, we examined the effects of resveratrol on cell self-renewal and differentiation of human mesenchymal stem cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at concentrations ranging from 0.1 to 10 µM after both short- and long-term exposure. Our results reveal that at 0.1 µM, resveratrol promotes cell self-renewal by inhibiting cellular senescence, whereas at 5 µM or above, resveratrol inhibits cell self-renewal by increasing senescence rate, cell doubling time and S-phase cell cycle arrest. At 1 µM, its effect on cell self-renewal is minimal but after long-term exposure it exerts an inhibitory effect, accompanied with increased senescence rate. At all concentrations, resveratrol promotes osteogenic differentiation in a dosage dependent manner, which is offset by its inhibitory effect on cell self-renewal at high concentrations. On the contrary, resveratrol suppresses adipogenic differentiation during short-term exposure but promotes this process after long-term exposure. Our study implicates that resveratrol is the most beneficial to stem cell development at 0.1 µM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its dosage dependent effect on hMSCs. PMID:22615926

  3. Age and dosage-level dependence of radium retention in beagles

    International Nuclear Information System (INIS)

    Parks, N.J.; Pool, R.R.; Williams, J.R.; Wolf, H.G.

    1978-01-01

    Radium retention was measured over the lifespan of 46 beagles exposed by eight semimonthly injections at 60 to 160, 120 to 220, or 435 to 535 days of age. Injection dosage levels ranged from 0.37 to 10 μCi of 226 Ra/kg. The fractional retention of each animal is described in terms of a modified power function, R = [(t + d)/d] - /sup b/. Young adult beagles (approximately equal to 10 kg) injected at a mean age (A) of 485 days with 226 Ra at dosage levels of 10, 3.3, 1.11, and 0.37 μCi/kg had mean values for d and b of [0.897; 0.187], [2.015; 0.206], [2.778; 0.257], and [3.894; 0.274], respectively. Juvenile beagles injected with 10 μCi/kg at A = 110 days (average weight approximately equal to 6 kg) and at A = 170 days (average weight approximately equal to 10 kg) had mean values for d and b of [137; 0.277] and [5.53; 0.086], respectively. The d values are geometric means and the units are days; b values are arithmetic means. The formula for deriving the age-dependent retention function for dogs is given. The beagle results were correlated with human data in terms of age-to-equivalent fraction of adult body calcium content and were used to construct a similar age-dependent retention function for chronically exposed people. The correlation of age-dependent retention functions for beagles and humans is used to estimate scaling factors between the two species for the fraction of injected dosage associated with bone for various ages of exposure

  4. Dependence of surface smoothing, sputtering and etching phenomena on cluster ion dosage

    CERN Document Server

    Song, J H; Choi, W K

    2002-01-01

    The dependence of surface smoothing and sputtering phenomena of Si (1 0 0) solid surfaces irradiated by CO sub 2 cluster ions on cluster-ion dosage was investigated using an atomic force microscope. The flux and total ion dosage of impinging cluster ions at the acceleration voltage of 50 kV were fixed at 10 sup 9 ions/cm sup 2 s and were scanned from 5x10 sup 1 sup 0 to 5x10 sup 1 sup 3 ions/cm sup 2 , respectively. The density of hillocks induced by cluster ion impact was gradually increased with the dosage up to 5x10 sup 1 sup 1 ions/cm sup 2 , which caused that the irradiated surface became rough from 0.4 to 1.24 nm in root-mean-square roughness (sigma sub r sub m sub s). At the boundary of the ion dosage of 10 sup 1 sup 2 ions/cm sup 2 , the density of the induced hillocks was decreased and sigma sub r sub m sub s was about 1.21 nm, not being deteriorated further. At the dosage of 5x10 sup 1 sup 3 ions/cm sup 2 , the induced hillocks completely disappeared and the surface became very flat as much as sigma...

  5. Dependence of 'CT clearance' on dosage and time

    International Nuclear Information System (INIS)

    Kaltenborn, H.A.; Klose, K.J.; Dexheimer, C.; Steinijans, V.

    1989-01-01

    The contrast medium dose used in CT renal function analysis corresponds to about 1 ml/kg body weight at a measurement interval of 5 or 10 minutes. In the present study the dependence of 'CT clearance' on dosage and time was examined in 12 healthy subjects. The amount of clearance was directly proportional to the employed contrast medium dose and to the length of the measurement interval. On account of the superior signal-to-noise ratio, the higher dose (1 ml/kg body weight) will continue to be prefered in future. The measurement interval can be limited to 10 minutes. (orig.) [de

  6. Mode of ATM-dependent suppression of chromosome translocation

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  7. ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

    Science.gov (United States)

    Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

    2006-12-01

    The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

  8. Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.

    Science.gov (United States)

    Yamashita, Teruhito; Uehara, Shunsuke; Udagawa, Nobuyuki; Li, Feng; Kadota, Shigetoshi; Esumi, Hiroyasu; Kobayashi, Yasuhiro; Takahashi, Naoyuki

    2014-01-01

    Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA), a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the pit

  9. Arctigenin Inhibits Osteoclast Differentiation and Function by Suppressing Both Calcineurin-Dependent and Osteoblastic Cell-Dependent NFATc1 Pathways

    Science.gov (United States)

    Yamashita, Teruhito; Uehara, Shunsuke; Udagawa, Nobuyuki; Li, Feng; Kadota, Shigetoshi; Esumi, Hiroyasu; Kobayashi, Yasuhiro; Takahashi, Naoyuki

    2014-01-01

    Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM) cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA), a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the pit

  10. Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways.

    Directory of Open Access Journals (Sweden)

    Teruhito Yamashita

    Full Text Available Arctigenin, a lignan-derived compound, is a constituent of the seeds of Arctium lappa. Arctigenin was previously shown to inhibit osteoclastogenesis; however, this inhibitory mechanism has yet to be elucidated. Here, we showed that arctigenin inhibited the action of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1, a key transcription factor for osteoclastogenesis. NFATc1 in osteoclast precursors was activated through two distinct pathways: the calcineurin-dependent and osteoblastic cell-dependent pathways. Among the several lignan-derived compounds examined, arctigenin most strongly inhibited receptor activator of nuclear factor κB ligand (RANKL-induced osteoclast-like cell formation in mouse bone marrow macrophage (BMM cultures, in which the calcineurin-dependent NFATc1 pathway was activated. Arctigenin suppressed neither the activation of nuclear factor κB and mitogen-activated protein kinases nor the up-regulation of c-Fos expression in BMMs treated with RANKL. However, arctigenin suppressed RANKL-induced NFATc1 expression. Interestingly, the treatment of osteoclast-like cells with arctigenin converted NFATc1 into a lower molecular weight species, which was translocated into the nucleus even in the absence of RANKL. Nevertheless, arctigenin as well as cyclosporin A (CsA, a calcineurin inhibitor, suppressed the NFAT-luciferase reporter activity induced by ionomycin and phorbol 12-myristate 13-acetate in BMMs. Chromatin immunoprecipitation analysis confirmed that arctigenin inhibited the recruitment of NFATc1 to the promoter region of the NFATc1 target gene. Arctigenin, but not CsA suppressed osteoclast-like cell formation in co-cultures of osteoblastic cells and bone marrow cells, in which the osteoblastic cell-dependent NFATc1 pathway was activated. The forced expression of constitutively active NFATc1 rescued osteoclastogenesis in BMM cultures treated with CsA, but not that treated with arctigenin. Arctigenin also suppressed the

  11. Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis

    Directory of Open Access Journals (Sweden)

    Ajantha Nadesalingam

    2018-03-01

    Full Text Available Tonicity of saline (NaCl is important in regulating cellular functions and homeostasis. Hypertonic saline is administered to treat many inflammatory diseases, including cystic fibrosis. Excess neutrophil extracellular trap (NET formation, or NETosis, is associated with many pathological conditions including chronic inflammation. Despite the known therapeutic benefits of hypertonic saline, its underlying mechanisms are not clearly understood. Therefore, we aimed to elucidate the effects of hypertonic saline in modulating NETosis. For this purpose, we purified human neutrophils and induced NETosis using agonists such as diacylglycerol mimetic phorbol myristate acetate (PMA, Gram-negative bacterial cell wall component lipopolysaccharide (LPS, calcium ionophores (A23187 and ionomycin from Streptomyces conglobatus, and bacteria (Pseudomonas aeruginosa and Staphylococcus aureus. We then analyzed neutrophils and NETs using Sytox green assay, immunostaining of NET components and apoptosis markers, confocal microscopy, and pH sensing reagents. This study found that hypertonic NaCl suppresses nicotinamide adenine dinucleotide phosphate oxidase (NADPH2 or NOX2-dependent NETosis induced by agonists PMA, Escherichia coli LPS (0111:B4 and O128:B12, and P. aeruginosa. Hypertonic saline also suppresses LPS- and PMA- induced reactive oxygen species production. It was determined that supplementing H2O2 reverses the suppressive effect of hypertonic saline on NOX2-dependent NETosis. Many of the aforementioned suppressive effects were observed in the presence of equimolar concentrations of choline chloride and osmolytes (d-mannitol and d-sorbitol. This suggests that the mechanism by which hypertonic saline suppresses NOX2-dependent NETosis is via neutrophil dehydration. Hypertonic NaCl does not significantly alter the intracellular pH of neutrophils. We found that hypertonic NaCl induces apoptosis while suppressing NOX2-dependent NETosis. In contrast, hypertonic

  12. Dosage-dependent role of Rac1 in podocyte injury

    Science.gov (United States)

    Wan, Xiaoyang; Lee, Mi-Sun

    2016-01-01

    Activation of small GTPase Rac1 in podocytes is associated with rodent models of kidney injury and familial nephrotic syndrome. Induced Rac1 activation in podocytes in transgenic mice results in rapid transient proteinuria and foot process effacement, but not glomerular sclerosis. Thus it remains an open question whether abnormal activation of Rac1 in podocytes is sufficient to cause permanent podocyte damage. Using a number of transgenic zebrafish models, we showed that moderate elevation of Rac1 activity in podocytes did not impair the glomerular filtration barrier but aggravated metronidazole-induced podocyte injury, while inhibition of Rac1 activity ameliorated metronidazole-induced podocyte injury. Furthermore, a further increase in Rac1 activity in podocytes was sufficient to cause proteinuria and foot process effacement, which resulted in edema and lethality in juvenile zebrafish. We also found that activation of Rac1 in podocytes significantly downregulated the expression of nephrin and podocin, suggesting an adverse effect of Rac1 on slit diaphragm protein expression. Taken together, our data have demonstrated a causal link between excessive Rac1 activity and podocyte injury in a dosage-dependent manner, and transgenic zebrafish of variable Rac1 activities in podocytes may serve as useful animal models for the study of Rac1-related podocytopathy. PMID:26792065

  13. A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

    Science.gov (United States)

    Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

    2012-10-05

    The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. A cluster-analytic profiling of heroin-dependent patients based on level, clinical adequacy, and patient-desired adjustment of buprenorphine dosage during buprenorphine-naloxone maintenance treatment in sixteen Spanish centers.

    Science.gov (United States)

    Alcaraz, Saul; González-Saiz, Francisco; Trujols, Joan; Vergara-Moragues, Esperanza; Siñol, Núria; Pérez de Los Cobos, José

    2018-06-01

    Buprenorphine dosage is a crucial factor influencing outcomes of buprenorphine treatment for heroin use disorders. Therefore, the aim of the present study is to identify naturally occurring profiles of heroin-dependent patients regarding individualized management of buprenorphine dosage in clinical practice of buprenorphine-naloxone maintenance treatment. 316 patients receiving buprenorphine-naloxone maintenance treatment were surveyed at 16 Spanish centers during the stabilization phase of this treatment. Patients were grouped using cluster analysis based on three key indicators of buprenorphine dosage management: dose, adequacy according to physician, and adjustment according to patient. The clusters obtained were compared regarding different facets of patient clinical condition. Four clusters were identified and labeled as follows (buprenorphine average dose and percentage of participants in each cluster are given in brackets): "Clinically Adequate and Adjusted to Patient Desired Low Dosage" (2.60 mg/d, 37.05%); "Clinically Adequate and Adjusted to Patient Desired High Dosage" (10.71 mg/d, 29.18%); "Clinically Adequate and Patient Desired Reduction of Low Dosage" (3.38 mg/d, 20.0%); and "Clinically Inadequate and Adjusted to Patient Desired Moderate Dosage" (7.55 mg/d, 13.77%). Compared to patients from the other three clusters, participants in the latter cluster reported more frequent use of heroin and cocaine during last week, lower satisfaction with buprenorphine-naloxone as a medication, higher prevalence of buprenorphine-naloxone adverse effects and poorer psychological adjustment. Our results show notable differences between clusters of heroin-dependent patients regarding buprenorphine dosage management. We also identified a group of patients receiving clinically inadequate buprenorphine dosage, which was related to poorer clinical condition. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis.

    Directory of Open Access Journals (Sweden)

    Takla Griss

    2015-12-01

    Full Text Available Metformin is a biguanide widely prescribed to treat Type II diabetes that has gained interest as an antineoplastic agent. Recent work suggests that metformin directly antagonizes cancer cell growth through its actions on complex I of the mitochondrial electron transport chain (ETC. However, the mechanisms by which metformin arrests cancer cell proliferation remain poorly defined. Here we demonstrate that the metabolic checkpoint kinases AMP-activated protein kinase (AMPK and LKB1 are not required for the antiproliferative effects of metformin. Rather, metformin inhibits cancer cell proliferation by suppressing mitochondrial-dependent biosynthetic activity. We show that in vitro metformin decreases the flow of glucose- and glutamine-derived metabolic intermediates into the Tricarboxylic Acid (TCA cycle, leading to reduced citrate production and de novo lipid biosynthesis. Tumor cells lacking functional mitochondria maintain lipid biosynthesis in the presence of metformin via glutamine-dependent reductive carboxylation, and display reduced sensitivity to metformin-induced proliferative arrest. Our data indicate that metformin inhibits cancer cell proliferation by suppressing the production of mitochondrial-dependent metabolic intermediates required for cell growth, and that metabolic adaptations that bypass mitochondrial-dependent biosynthesis may provide a mechanism of tumor cell resistance to biguanide activity.

  16. Purifying Selection Maintains Dosage-Sensitive Genes during Degeneration of the Threespine Stickleback Y Chromosome

    Science.gov (United States)

    White, Michael A.; Kitano, Jun; Peichel, Catherine L.

    2015-01-01

    Sex chromosomes are subject to unique evolutionary forces that cause suppression of recombination, leading to sequence degeneration and the formation of heteromorphic chromosome pairs (i.e., XY or ZW). Although progress has been made in characterizing the outcomes of these evolutionary processes on vertebrate sex chromosomes, it is still unclear how recombination suppression and sequence divergence typically occur and how gene dosage imbalances are resolved in the heterogametic sex. The threespine stickleback fish (Gasterosteus aculeatus) is a powerful model system to explore vertebrate sex chromosome evolution, as it possesses an XY sex chromosome pair at relatively early stages of differentiation. Using a combination of whole-genome and transcriptome sequencing, we characterized sequence evolution and gene expression across the sex chromosomes. We uncovered two distinct evolutionary strata that correspond with known structural rearrangements on the Y chromosome. In the oldest stratum, only a handful of genes remain, and these genes are under strong purifying selection. By comparing sex-linked gene expression with expression of autosomal orthologs in an outgroup, we show that dosage compensation has not evolved in threespine sticklebacks through upregulation of the X chromosome in males. Instead, in the oldest stratum, the genes that still possess a Y chromosome allele are enriched for genes predicted to be dosage sensitive in mammals and yeast. Our results suggest that dosage imbalances may have been avoided at haploinsufficient genes by retaining function of the Y chromosome allele through strong purifying selection. PMID:25818858

  17. Determining S-1 dosage at hospitals prioritizing cancer chemotherapy

    International Nuclear Information System (INIS)

    Morimoto, Shigefumi; Kitada, Noriaki; Anami, Setsuko

    2008-01-01

    Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. At hospitals giving priority to chemotherapy, it became clear that appropriate treatment was promoted by decreasing. The individual target dosage on the basis of daily medical examination. (author)

  18. Foam suppression in overloaded manure-based biogas reactors using antifoaming agents

    DEFF Research Database (Denmark)

    Kougias, Panagiotis; Boe, Kanokwan; Tsapekos, Panagiotis

    2014-01-01

    Foam control is an imperative need in biogas plants, as foaming is a major operational problem. In the present study, the effect of oils (rapeseed oil, oleic acid, and octanoic acid) and tributylphosphate on foam reduction and process performance in batch and continuous manure-based biogas reactors...... was investigated. The compounds were tested in dosages of 0.05%, 0.1% and 0.5% v/vfeed. The results showed that rapeseed oil was most efficient to suppress foam at the dosage of 0.05% and 0.1% v/vfeed, while octanoic acid was most efficient to suppress foam at dosage of 0.5% v/vfeed. Moreover, the addition...... of rapeseed oil also increased methane yield. In contrast, tributylphosphate, which was very efficient antifoam, was found to be inhibitory to the biogas process. © 2013 Elsevier Ltd....

  19. Prediction suppression in monkey inferotemporal cortex depends on the conditional probability between images.

    Science.gov (United States)

    Ramachandran, Suchitra; Meyer, Travis; Olson, Carl R

    2016-01-01

    When monkeys view two images in fixed sequence repeatedly over days and weeks, neurons in area TE of the inferotemporal cortex come to exhibit prediction suppression. The trailing image elicits only a weak response when presented following the leading image that preceded it during training. Induction of prediction suppression might depend either on the contiguity of the images, as determined by their co-occurrence and captured in the measure of joint probability P(A,B), or on their contingency, as determined by their correlation and as captured in the measures of conditional probability P(A|B) and P(B|A). To distinguish between these possibilities, we measured prediction suppression after imposing training regimens that held P(A,B) constant but varied P(A|B) and P(B|A). We found that reducing either P(A|B) or P(B|A) during training attenuated prediction suppression as measured during subsequent testing. We conclude that prediction suppression depends on contingency, as embodied in the predictive relations between the images, and not just on contiguity, as embodied in their co-occurrence. Copyright © 2016 the American Physiological Society.

  20. Transverse momentum dependence of charmonium suppression in Pb-Pb collisions at the CERN SPS

    CERN Document Server

    Alessandro, Bruno; Arnaldi, R; Atayan, M; Beolè, S; Boldea, V; Bordalo, P; Borges, G; Castanier, C; Castor, J; Chaurand, B; Cheynis, B; Chiavassa, E; Cicalò, C; Comets, M P; Constantinescu, S; Cormick, M M; Cortese, P; De Falco, A; De Marco, N; Dellacasa, G; Devaux, A; Dita, S; Fargeix, J; Force, P; Gallio, M; Gerschel, C; Giubellino, P; Golubeva, M B; Grigorian, A A; Grigorian, S; Guber, F F; Guichard, A; Gulkanian, H R; Idzik, M; Jouan, D; Karavitcheva, T L; Kluberg, L; Kurepin, A B; Le Bornec, Y; Lourenço, C; Marzari-Chiesa, A; Masera, M; Masoni, A; Monteno, M; Musso, A; Petiau, P; Piccotti, A; Pizzi, J R; Prino, F; Puddu, G; Quintans, C; Ramello, L; Ramos, S; Riccati, L; Santos, H; Saturnini, P; Scomparin, E; Serci, S; Shahoyan, R; Sigaudo, F; Sitta, M; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, E; Villatte, L; Willis, N; Wu, T

    2005-01-01

    Charmonium suppression in Pb-Pb collisions at 158 GeV/c per nucleon is investigated in detail with the study of the transverse momentum distributions of J/ psi as a function of the centrality of the collision. It is shown that the observed J/ psi suppression in Pb-Pb interactions is particularly significant mainly at low transverse momentum where it strongly depends on centrality. For peripheral Pb- Pb collisions, the transverse momentum dependence of the J/ psi cross section is, as a function of centrality, qualitatively similar to the dependence observed in p-A and S-U collisions. Comparing peripheral and central Pb-Pb collisions, the data show a relative suppression in the whole p/sub T/ range although its amplitude significantly decreases with increasing p/sub T/ and becomes almost p/sub T/ independent for the highest p/sub T/ values.

  1. The Role of Thought Suppression, Meta-Cognitive Factors and Negative Emotions in Prediction of Substance Dependency Disorder

    Directory of Open Access Journals (Sweden)

    Omid Saed

    2011-08-01

    Full Text Available Introduction: This study investigated the role of thought suppression, meta- cognitive factors, and negative emotions in predicting of substance dependency disorder. Method: Subjects were 70 patients with substance dependence disorder and 70 normal individuals (total 140. Substance dependants were selected of outpatient treatment centers and the normal sample was selected of the general population too. Sampling methods in both samples were convenience sampling. All people were assessed by MCQ-30, White Bear Suppression Inventory, and Beck’s Anxiety and Depression Questionnaires. For data analysis, discriminant analysis were used. Results: Negative meta-cognitive beliefs about worry, depression, and thought suppression were the most significant predictors of substance dependence disorder. Conclusion: Through meta-cognitive beliefs, thought suppression and negative emotion (especially depression, substance dependency disorder can be predicted. Based on this model can be used to take a substance dependency disorder prevention approach and psychotherapy approach (based on cognitive and meta-cognitive therapies. In addition, the findings of this research can be applied in clinical and counseling environments to help substance dependant clients.

  2. Special regulatory T-cell review: T-cell dependent suppression revisited.

    Science.gov (United States)

    Basten, Antony; Fazekas de St Groth, Barbara

    2008-01-01

    The concept of T-cell dependent regulation of immune responses has been a central tenet of immunological thinking since the delineation of the two cell system in the 1960s. Indeed T-cell dependent suppression was discovered before MHC restriction. When reviewing the data from the original wave of suppression, it is intriguing to reflect not just on the decline and fall of suppressor T cells in the 1980s, but on their equally dramatic return to respectability over the past decade. Hopefully their resurgence will be supported by solid mechanistic data that will underpin their central place in our current and future understanding of the immune system. Cannon to right of them, Cannon to left of them, Cannon in front of them Volley'd and thunder'd Storm'd at with shot and shell, Boldly they rode and well, Into the jaws of Death, Into the mouth of Hell, Rode the six hundred (suppressionists). (Adapted from The Charge of the Light Brigade, Alfred, Lord Tennyson)

  3. TIME-DEPENDENT SUPPRESSION OF OSCILLATORY POWER IN EVOLVING SOLAR MAGNETIC FIELDS

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, S. Krishna; Jess, D.B.; Keys, P.H. [Astrophysics Research Centre, School of Mathematics and Physics, Queen’s University Belfast, Belfast, BT7 1NN (United Kingdom); Jain, R., E-mail: krishna.prasad@qub.ac.uk [School of Mathematics and Statistics, University of Sheffield, Sheffield S3 7RH (United Kingdom)

    2016-05-20

    Oscillation amplitudes are generally smaller within magnetically active regions like sunspots and plage when compared to their surroundings. Such magnetic features, when viewed in spatially resolved power maps, appear as regions of suppressed power due to reductions in the oscillation amplitudes. Employing high spatial- and temporal-resolution observations from the Dunn Solar Telescope (DST) in New Mexico, we study the power suppression in a region of evolving magnetic fields adjacent to a pore. By utilizing wavelet analysis, we study for the first time how the oscillatory properties in this region change as the magnetic field evolves with time. Image sequences taken in the blue continuum, G-band, Ca ii K, and H α filters were used in this study. It is observed that the suppression found in the chromosphere occupies a relatively larger area, confirming previous findings. Also, the suppression is extended to structures directly connected to the magnetic region, and is found to get enhanced as the magnetic field strength increased with time. The dependence of the suppression on the magnetic field strength is greater at longer periods and higher formation heights. Furthermore, the dominant periodicity in the chromosphere was found to be anti-correlated with increases in the magnetic field strength.

  4. Doubled dosage of sofosbuviris expected for inhibiting Zika virus infection

    Institute of Scientific and Technical Information of China (English)

    Somsri Wiwanitkit; Viroj Wiwanitkit

    2017-01-01

    Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus (HCV) for a few years. New researches support that sofosbuvir might be useful for the management of Zika virus infection. Based on the pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase (RdRp or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus infection. Here, the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection. Based on the modeling study, if sofosbuvir is assigned for management of Zika virus infection, doubled dosage of the present dosage for hepatitis C management is recommended.

  5. Transverse-momentum and collision-energy dependence of high-pT hadron suppression in Au+Au collisions at ultrarelativistic energies.

    Science.gov (United States)

    Adams, J; Adler, C; Aggarwal, M M; Ahammed, Z; Amonett, J; Anderson, B D; Anderson, M; Arkhipkin, D; Averichev, G S; Badyal, S K; Balewski, J; Barannikova, O; Barnby, L S; Baudot, J; Bekele, S; Belaga, V V; Bellwied, R; Berger, J; Bezverkhny, B I; Bhardwaj, S; Bhaskar, P; Bhati, A K; Bichsel, H; Billmeier, A; Bland, L C; Blyth, C O; Bonner, B E; Botje, M; Boucham, A; Brandin, A; Bravar, A; Cadman, R V; Cai, X Z; Caines, H; Calderón de la Barca Sánchez, M; Carroll, J; Castillo, J; Castro, M; Cebra, D; Chaloupka, P; Chattopadhyay, S; Chen, H F; Chen, Y; Chernenko, S P; Cherney, M; Chikanian, A; Choi, B; Christie, W; Coffin, J P; Cormier, T M; Cramer, J G; Crawford, H J; Das, D; Das, S; Derevschikov, A A; Didenko, L; Dietel, T; Dong, X; Draper, J E; Drees, K A; Du, F; Dubey, A K; Dunin, V B; Dunlop, J C; Dutta Majumdar, M R; Eckardt, V; Efimov, L G; Emelianov, V; Engelage, J; Eppley, G; Erazmus, B; Fachini, P; Faine, V; Faivre, J; Fatemi, R; Filimonov, K; Filip, P; Finch, E; Fisyak, Y; Flierl, D; Foley, K J; Fu, J; Gagliardi, C A; Ganti, M S; Gagunashvili, N; Gans, J; Gaudichet, L; Germain, M; Geurts, F; Ghazikhanian, V; Ghosh, P; Gonzalez, J E; Grachov, O; Grigoriev, V; Gronstal, S; Grosnick, D; Guedon, M; Guertin, S M; Gupta, A; Gushin, E; Gutierrez, T D; Hallman, T J; Hardtke, D; Harris, J W; Heinz, M; Henry, T W; Heppelmann, S; Herston, T; Hippolyte, B; Hirsch, A; Hjort, E; Hoffmann, G W; Horsley, M; Huang, H Z; Huang, S L; Humanic, T J; Igo, G; Ishihara, A; Jacobs, P; Jacobs, W W; Janik, M; Johnson, I; Jones, P G; Judd, E G; Kabana, S; Kaneta, M; Kaplan, M; Keane, D; Kiryluk, J; Kisiel, A; Klay, J; Klein, S R; Klyachko, A; Kollegger, T; Konstantinov, A S; Kopytine, M; Kotchenda, L; Kovalenko, A D; Kramer, M; Kravtsov, P; Krueger, K; Kuhn, C; Kulikov, A I; Kumar, A; Kunde, G J; Kunz, C L; Kutuev, R Kh; Kuznetsov, A A; Lamont, M A C; Landgraf, J M; Lange, S; Lansdell, C P; Lasiuk, B; Laue, F; Lauret, J; Lebedev, A; Lednický, R; Leontiev, V M; LeVine, M J; Li, C; Li, Q; Lindenbaum, S J; Lisa, M A; Liu, F; Liu, L; Liu, Z; Liu, Q J; Ljubicic, T; Llope, W J; Long, H; Longacre, R S; Lopez-Noriega, M; Love, W A; Ludlam, T; Lynn, D; Ma, J; Ma, Y G; Magestro, D; Mahajan, S; Mangotra, L K; Mahapatra, D P; Majka, R; Manweiler, R; Margetis, S; Markert, C; Martin, L; Marx, J; Matis, H S; Matulenko, Yu A; McShane, T S; Meissner, F; Melnick, Yu; Meschanin, A; Messer, M; Miller, M L; Milosevich, Z; Minaev, N G; Mironov, C; Mishra, D; Mitchell, J; Mohanty, B; Molnar, L; Moore, C F; Mora-Corral, M J; Morozov, V; de Moura, M M; Munhoz, M G; Nandi, B K; Nayak, S K; Nayak, T K; Nelson, J M; Nevski, P; Nikitin, V A; Nogach, L V; Norman, B; Nurushev, S B; Odyniec, G; Ogawa, A; Okorokov, V; Oldenburg, M; Olson, D; Paic, G; Pandey, S U; Pal, S K; Panebratsev, Y; Panitkin, S Y; Pavlinov, A I; Pawlak, T; Perevoztchikov, V; Peryt, W; Petrov, V A; Phatak, S C; Picha, R; Planinic, M; Pluta, J; Porile, N; Porter, J; Poskanzer, A M; Potekhin, M; Potrebenikova, E; Potukuchi, B V K S; Prindle, D; Pruneau, C; Putschke, J; Rai, G; Rakness, G; Raniwala, R; Raniwala, S; Ravel, O; Ray, R L; Razin, S V; Reichhold, D; Reid, J G; Renault, G; Retiere, F; Ridiger, A; Ritter, H G; Roberts, J B; Rogachevski, O V; Romero, J L; Rose, A; Roy, C; Ruan, L J; Rykov, V; Sahoo, R; Sakrejda, I; Salur, S; Sandweiss, J; Savin, I; Schambach, J; Scharenberg, R P; Schmitz, N; Schroeder, L S; Schweda, K; Seger, J; Seliverstov, D; Seyboth, P; Shahaliev, E; Shao, M; Sharma, M; Shestermanov, K E; Shimanskii, S S; Singaraju, R N; Simon, F; Skoro, G; Smirnov, N; Snellings, R; Sood, G; Sorensen, P; Sowinski, J; Spinka, H M; Srivastava, B; Stanislaus, S; Stock, R; Stolpovsky, A; Strikhanov, M; Stringfellow, B; Struck, C; Suaide, A A P; Sugarbaker, E; Suire, C; Sumbera, M; Surrow, B; Symons, T J M; Szanto de Toledo, A; Szarwas, P; Tai, A; Takahashi, J; Tang, A H; Thein, D; Thomas, J H; Tikhomirov, V; Tokarev, M; Tonjes, M B; Trainor, T A; Trentalange, S; Tribble, R E; Trivedi, M D; Trofimov, V; Tsai, O; Ullrich, T; Underwood, D G; Van Buren, G; VanderMolen, A M; Vasiliev, A N; Vasiliev, M; Vigdor, S E; Viyogi, Y P; Voloshin, S A; Waggoner, W; Wang, F; Wang, G; Wang, X L; Wang, Z M; Ward, H; Watson, J W; Wells, R; Westfall, G D; Whitten, C; Wieman, H; Willson, R; Wissink, S W; Witt, R; Wood, J; Wu, J; Xu, N; Xu, Z; Xu, Z Z; Yakutin, A E; Yamamoto, E; Yang, J; Yepes, P; Yurevich, V I; Zanevski, Y V; Zborovský, I; Zhang, H; Zhang, H Y; Zhang, W M; Zhang, Z P; Zołnierczuk, P A; Zoulkarneev, R; Zoulkarneeva, J; Zubarev, A N

    2003-10-24

    We report high statistics measurements of inclusive charged hadron production in Au+Au and p+p collisions at sqrt[s(NN)]=200 GeV. A large, approximately constant hadron suppression is observed in central Au+Au collisions for 5dependence of the yields and the centrality and p(T) dependence of the suppression provide stringent constraints on theoretical models of suppression. Models incorporating initial-state gluon saturation or partonic energy loss in dense matter are largely consistent with observations. We observe no evidence of p(T)-dependent suppression, which may be expected from models incorporating jet attenuation in cold nuclear matter or scattering of fragmentation hadrons.

  6. Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis.

    Science.gov (United States)

    Iizuka, Masahiro; Etou, Takeshi; Kumagai, Makoto; Matsuoka, Atsushi; Numata, Yuka; Sagara, Shiho

    2017-10-15

    Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed "long-interval cytapheresis (LI-CAP)", in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (psteroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC.

  7. Suppressing gravitino thermal production with a temperature-dependent messenger coupling

    International Nuclear Information System (INIS)

    Badziak, Marcin; Dalianis, Ioannis; Lalak, Zygmunt

    2016-01-01

    We show that the constraints on GMSB theories from the gravitino cosmology can be significantly relaxed if the messenger-spurion coupling is temperature dependent. We demonstrate this novel mechanism in a scenario in which this coupling depends on the VEV of an extra singlet field S that interacts with the thermalized plasma which can result in a significantly suppressed gravitino production rate. In such a scenario the relic gravitino abundance is determined by the thermal dynamics of the S field and it is easy to fit the observed dark matter abundance evading the stringent constraints on the reheating temperature, thus making gravitino dark matter consistent with thermal leptogenesis.

  8. Thought suppression, impaired regulation of urges, and Addiction-Stroop predict affect-modulated cue-reactivity among alcohol dependent adults.

    Science.gov (United States)

    Garland, Eric L; Carter, Kristin; Ropes, Katie; Howard, Matthew O

    2012-01-01

    Abstinent alcohol dependent individuals commonly employ thought suppression to cope with stress and intrusive cognitions about alcohol. This strategy may inadvertently bias attention towards alcohol-related stimuli while depleting neurocognitive resources needed to regulate urges, manifested as decreased heart rate variability (HRV) responsivity to alcohol cues. The present study tested the hypothesis that trait and state thought suppression, impaired regulation of urges, and alcohol attentional bias as measured by the Addiction-Stroop would have significant effects on the HRV responsivity of 58 adults in residential treatment for alcohol dependence (mean age=39.6 ± 9.4, 81% female) who participated in an affect-modulated cue-reactivity protocol. Regression analyses controlling for age, level of pre-treatment alcohol consumption, and baseline HRV indicated that higher levels of trait thought suppression, impaired regulation of alcohol urges, and attentional fixation on alcohol cues were associated with lower HRV responsivity during stress-primed alcohol cue-exposure. Moreover, there was a significant state × trait suppression interaction on HRV cue-responsivity, such that alcohol dependent persons reporting high levels of state and trait suppression exhibited less HRV during cue-exposure than persons reporting low levels of state and trait suppression. Results suggest that chronic thought suppression taxes regulatory resources reflected in reduced HRV responsivity, an effect that is particularly evident when high trait suppressors engage in intensive suppression of drinking-related thoughts under conditions of stress. Treatment approaches that offer effective alternatives to the maladaptive strategy of suppressing alcohol urges may be crucial for relapse prevention. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression.

    Directory of Open Access Journals (Sweden)

    Alejo Efeyan

    Full Text Available Recent studies in human fibroblasts have provided a new general paradigm of tumor suppression according to which oncogenic signaling produces DNA damage and this, in turn, results in ATM/p53-dependent cellular senescence. Here, we have tested this model in a variety of murine experimental systems. Overexpression of oncogenic Ras in murine fibroblasts efficiently induced senescence but this occurred in the absence of detectable DNA damage signaling, thus suggesting a fundamental difference between human and murine cells. Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling. Accordingly, K-Ras-driven adenomas were also senescent in Atm-null mice, and the tumorigenic progression of these lesions was only modestly accelerated by Atm-deficiency. Finally, we have examined chemically-induced fibrosarcomas, which possess a persistently activated DNA damage response and are highly sensitive to the activity of p53. We found that the absence of Atm favored genomic instability in the resulting tumors, but did not affect the persistent DNA damage response and did not impair p53-dependent tumor suppression. All together, we conclude that oncogene-induced senescence in mice may occur in the absence of a detectable DNA damage response. Regarding murine Atm, our data suggest that it plays a minor role in oncogene-induced senescence or in p53-dependent tumor suppression, being its tumor suppressive activity probably limited to the maintenance of genomic stability.

  10. Tissue- and stage-dependent dosage compensation on the Neo-X chromosome in drosophila pseudoobscura

    KAUST Repository

    Nozawa, Masafumi; Fukuda, Nana; Ikeo, Kazuho; Gojobori, Takashi

    2013-01-01

    Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly

  11. Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.

    Science.gov (United States)

    Lofwall, Michelle R; Babalonis, Shanna; Nuzzo, Paul A; Elayi, Samy Claude; Walsh, Sharon L

    2016-07-01

    The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal. Twelve opioid dependent adults participated in this 5-week, inpatient, double-blind, randomized, placebo-controlled study. Volunteers were maintained on double-blind oxycodone (30mg oral, four times/day) and participated in a training session followed by 7 experimental sessions, each testing a single oral test dose (placebo, oxycodone 30 and 60mg, dronabinol 5, 10, 20, and 30mg [decreased from 40mg]). Placebo was substituted for oxycodone maintenance doses for 21h before each session in order to produce measurable opioid withdrawal. Outcomes included observer- and participant-ratings of opioid agonist, opioid withdrawal and psychomotor/cognitive performance. Oxycodone produced prototypic opioid agonist effects (i.e. suppressing withdrawal and increasing subjective effects indicative of abuse liability). Dronabinol 5 and 10mg produced effects most similar to placebo, while the 20 and 30mg doses produced modest signals of withdrawal suppression that were accompanied by dose-related increases in high, sedation, bad effects, feelings of heart racing, and tachycardia. Dronabinol was not liked more than placebo, showed some impairment in cognitive performance, and was identified as marijuana with increasing dose. CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Administered activity of Tc-99m MDP for bone scintigraphy, standard or individual dosage?

    International Nuclear Information System (INIS)

    Vestergren, E.; Gretarsdottir, J.; Jacobsson, L.

    2002-01-01

    gives no body weight dependence of SPINEmax. For all methods the variation in SPINEmax is large, with a coefficient of variation of approximately 25%. For the other image quality parameter, FEMURmax, it is the dosage method proportional to height which gives no dependence of patient size. Conclusion: It is possible to reduce the variations in count level (image quality) for bone scan patients using individual dosage based on body size. However, most variations remain because of other individual factors

  13. Dosage and cell line dependent inhibitory effect of bFGF supplement in human pluripotent stem cell culture on inactivated human mesenchymal stem cells.

    Science.gov (United States)

    Quang, Tara; Marquez, Maribel; Blanco, Giselle; Zhao, Yuanxiang

    2014-01-01

    Many different culture systems have been developed for expanding human pluripotent stem cells (hESCs and hiPSCs). In general, 4-10 ng/ml of bFGF is supplemented in culture media in feeder-dependent systems regardless of feeder cell types, whereas in feeder-free systems, up to 100 ng/ml of bFGF is required for maintaining long-term culture on various substrates. The amount of bFGF required in native hESCs growth niche is unclear. Here we report using inactivated adipose-derived human mesenchymal stem cells as feeder cells to examine long-term parallel cultures of two hESCs lines (H1 and H9) and one hiPSCs line (DF19-9-7T) in media supplemented with 0, 0.4 or 4 ng/ml of bFGF for up to 23 passages, as well as parallel cultures of H9 and DF19 in media supplemented with 4, 20 or 100 ng/ml bFGF for up to 13 passages for comparison. Across all cell lines tested, bFGF supplement demonstrated inhibitory effect over growth expansion, single cell colonization and recovery from freezing in a dosage dependent manner. In addition, bFGF exerted differential effects on different cell lines, inducing H1 and DF19 differentiation at 4 ng/ml or higher, while permitting long-term culture of H9 at the same concentrations with no apparent dosage effect. Pluripotency was confirmed for all cell lines cultured in 0, 0.4 or 4 ng/ml bFGF excluding H1-4 ng, as well as H9 cultured in 4, 20 and 100 ng/ml bFGF. However, DF19 demonstrated similar karyotypic abnormality in both 0 and 4 ng/ml bFGF media while H1 and H9 were karyotypically normal in 0 ng/ml bFGF after long-term culture. Our results indicate that exogenous bFGF exerts dosage and cell line dependent effect on human pluripotent stem cells cultured on mesenchymal stem cells, and implies optimal use of bFGF in hESCs/hiPSCs culture should be based on specific cell line and its culture system.

  14. Jet suppression and the flavor dependence of partonic energy loss with ATLAS

    Energy Technology Data Exchange (ETDEWEB)

    Kosek, Tomas

    2016-12-15

    In relativistic heavy ion collisions, a hot medium with a high density of unscreened color charges is produced. One manifestation of the energy loss of jets propagating through the medium is a lower yield of jets and hadrons emerging from this medium than expected in the absence of medium effects. Therefore modifications of the jet yield are directly sensitive to the energy loss mechanism. Furthermore, jets with different flavor content are expected to be affected by the medium in different ways. In this publication, the latest ATLAS results on single hadron suppression along with the complementary measurements of single jet suppression are presented. Rapidity dependence, which is sensitive to the relative energy loss between quark and gluon jets, is discussed. Finally, a new measurement of jet fragmentation functions is presented.

  15. Genomic structural variation-mediated allelic suppression causes hybrid male sterility in rice.

    Science.gov (United States)

    Shen, Rongxin; Wang, Lan; Liu, Xupeng; Wu, Jiang; Jin, Weiwei; Zhao, Xiucai; Xie, Xianrong; Zhu, Qinlong; Tang, Huiwu; Li, Qing; Chen, Letian; Liu, Yao-Guang

    2017-11-03

    Hybrids between divergent populations commonly show hybrid sterility; this reproductive barrier hinders hybrid breeding of the japonica and indica rice (Oryza sativa L.) subspecies. Here we show that structural changes and copy number variation at the Sc locus confer japonica-indica hybrid male sterility. The japonica allele, Sc-j, contains a pollen-essential gene encoding a DUF1618-domain protein; the indica allele, Sc-i, contains two or three tandem-duplicated ~ 28-kb segments, each carrying an Sc-j-homolog with a distinct promoter. In Sc-j/Sc-i hybrids, the high-expression of Sc-i in sporophytic cells causes suppression of Sc-j expression in pollen and selective abortion of Sc-j-pollen, leading to transmission ratio distortion. Knocking out one or two of the three Sc-i copies by CRISPR/Cas9 rescues Sc-j expression and male fertility. Our results reveal the gene dosage-dependent allelic suppression as a mechanism of hybrid incompatibility, and provide an effective approach to overcome the reproductive barrier for hybrid breeding.

  16. Memory suppression trades prolonged fear and sleep-dependent fear plasticity for the avoidance of current fear

    Science.gov (United States)

    Kuriyama, Kenichi; Honma, Motoyasu; Yoshiike, Takuya; Kim, Yoshiharu

    2013-07-01

    Sleep deprivation immediately following an aversive event reduces fear by preventing memory consolidation during homeostatic sleep. This suggests that acute insomnia might act prophylactically against the development of posttraumatic stress disorder (PTSD) even though it is also a possible risk factor for PTSD. We examined total sleep deprivation and memory suppression to evaluate the effects of these interventions on subsequent aversive memory formation and fear conditioning. Active suppression of aversive memory impaired retention of event memory. However, although the remembered fear was more reduced in sleep-deprived than sleep-control subjects, suppressed fear increased, and seemed to abandon the sleep-dependent plasticity of fear. Active memory suppression, which provides a psychological model for Freud's ego defense mechanism, enhances fear and casts doubt on the potential of acute insomnia as a prophylactic measure against PTSD. Our findings bring into question the role of sleep in aversive-memory consolidation in clinical PTSD pathophysiology.

  17. Competition-strength-dependent ground suppression in figure-ground perception.

    Science.gov (United States)

    Salvagio, Elizabeth; Cacciamani, Laura; Peterson, Mary A

    2012-07-01

    Figure-ground segregation is modeled as inhibitory competition between objects that might be perceived on opposite sides of borders. The winner is the figure; the loser is suppressed, and its location is perceived as shapeless ground. Evidence of ground suppression would support inhibitory competition models and would contribute to explaining why grounds are shapeless near borders shared with figures, yet such evidence is scarce. We manipulated whether competition from potential objects on the ground side of figures was high (i.e., portions of familiar objects were potentially present there) or low (novel objects were potentially present). We predicted that greater competition would produce more ground suppression. The results of two experiments in which suppression was assessed via judgments of the orientation of target bars confirmed this prediction; a third experiment showed that ground suppression is short-lived. Our findings support inhibitory competition models of figure assignment, in particular, and models of visual perception entailing feedback, in general.

  18. METCAM/MUC18 promoted tumorigenesis of human breast cancer SK-BR-3 cells in a dosage-specific manner.

    Science.gov (United States)

    Huang, Chang-Yu; Wu, Guang-Jer

    2016-04-01

    Overexpression of METCAM/MUC18, an immunoglobulin-like cell-adhesion molecule, promotes tumorigenesis and progression of human breast cancer cells. We also observed an intriguing phenomenon that a high-expressing SK-BR-3 clone manifested a transient tumor suppression effect in vivo. The purpose of this study was to understand if this was caused by clonal variation, METCAM/MUC18-dosage effect, or the number of cells injected. Several G418-resistant clones of SK-BR-3, expressing different levels of METCAM/MUC18, were obtained for testing effects of human METCAM/MUC18 on in vitro motility, invasiveness, and anchorage-independent colony formation (in vitro tumorigenicity) and in vivo tumorigenesis in female Balb/C athymic nude mice. Tumor sections were made for histology and immunohistochemistry analyses, and tumor lysates for Western blot analysis to determine the effects of human METCAM/MUC18 expression on levels of various downstream effectors. METCAM/MUC18 promoted in vitro motility, invasiveness, and in vitro tumorigenicity of SK-BR-3 cells in a dosage-specific manner. Overexpression of METCAM/MUC18 could promote in vivo tumorigenesis of SK-BR-3 cells even when one tenth of the previously used cell number (5 × 10(5)) was injected and in vivo tumorigenesis of SK-BR-3 cells was directly proportional to the dosage of the protein. The previously observed transient tumor suppression effect from the same clone was no longer observed. The downstream effector, such as phospho-AKT/AKT ratio, was elevated in the tumors. Transient suppression observed previously in the clone was caused by injection of a high cell number (2 × 10(6)-5 × 10(6)). METCAM/MUC18 positively promotes tumorigenesis of SK-BR-3 cells by increasing the survival and proliferation pathway. Copyright © 2016. Published by Elsevier B.V.

  19. Study on the immunological suppressive mechanisms of the cyclophosphamide-administration and total body irradiation

    International Nuclear Information System (INIS)

    Wakizaka, Yoshitaka; Uchino, Junichi; Yang, Zi-Bo.

    1994-01-01

    High dose-cyclophosphamide (CP) administration and total body irradiation (TBI) are often used for bone marrow transplantation in order to eradicate the residual tumor cells and to induce the immunological tolerance in the recipients. But CP is difficult to use as an immunosuppressant because this drug has indefinite effects on host's immune status depending on the dose, i.e. augment the humoral antibody production in small dosage and inhibit the rejective reaction in large dosage. Thus we study on the immunological mechanisms of this drug and the TBI used often with CP for bone marrow transplantation in leukemic patients. 150 mg/kg of CP was administered via tail vein, and 3 Gy (300 rads) of X-ray was irradiated. CP could suppress the host's cellular immunity within 5 days after administration but TBI could within 3 days. Reversely, CP augmented the cellular immunity since 5 days after treatment. CP damaged the IL-2 production irreversibely, but IL-3 production was inhibited by CP for only a few days and recovered rapidly. These characters were thought to be a big help for the implantation and development of the multipotent stem cells in the recipient's body after transplantation. (author)

  20. X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila.

    Science.gov (United States)

    Larschan, Erica; Bishop, Eric P; Kharchenko, Peter V; Core, Leighton J; Lis, John T; Park, Peter J; Kuroda, Mitzi I

    2011-03-03

    The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.

  1. Burst-Suppression Ratio on Electrocorticography Depends on Interelectrode Distance

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Calin, Alexandru; Kumaraswamy, Vishakhadatta M.

    2016-01-01

    Introduction: With deepening of anesthesia-induced comatose states, the EEG becomes fragmented by increasing periods of suppression. When measured from conventional EEG recordings, the binary burst-suppression signal (BS) appears similar across the scalp. As such, the BS ratio (BSR), quantifying...

  2. Condensin-driven remodelling of X chromosome topology during dosage compensation

    Science.gov (United States)

    Crane, Emily; Bian, Qian; McCord, Rachel Patton; Lajoie, Bryan R.; Wheeler, Bayly S.; Ralston, Edward J.; Uzawa, Satoru; Dekker, Job; Meyer, Barbara J.

    2015-07-01

    The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure. Here we perform genome-wide chromosome conformation capture analysis, fluorescent in situ hybridization (FISH), and RNA-seq to obtain comprehensive three-dimensional (3D) maps of the Caenorhabditis elegans genome and to dissect X chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X (rex sites) to reduce chromosome-wide gene expression by half. Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes. By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (~1 Mb) resembling mammalian topologically associating domains (TADs). TADs on X chromosomes have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X chromosomes coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-dependent long-range interactions, with the most frequent interactions occurring between rex sites at DCC-dependent TAD boundaries. These results imply that the DCC reshapes the topology of X chromosomes by forming new TAD boundaries and reinforcing weak boundaries through interactions between its highest-affinity binding sites. As this model predicts, deletion of an endogenous rex site at a DCC-dependent TAD boundary using

  3. Role of cyclic nucleotide-dependent actin cytoskeletal dynamics:Ca(2+](i and force suppression in forskolin-pretreated porcine coronary arteries.

    Directory of Open Access Journals (Sweden)

    Kyle M Hocking

    Full Text Available Initiation of force generation during vascular smooth muscle contraction involves a rise in intracellular calcium ([Ca(2+]i and phosphorylation of myosin light chains (MLC. However, reversal of these two processes alone does not account for the force inhibition that occurs during relaxation or inhibition of contraction, implicating that other mechanisms, such as actin cytoskeletal rearrangement, play a role in the suppression of force. In this study, we hypothesize that forskolin-induced force suppression is dependent upon changes in actin cytoskeletal dynamics. To focus on the actin cytoskeletal changes, a physiological model was developed in which forskolin treatment of intact porcine coronary arteries (PCA prior to treatment with a contractile agonist resulted in complete suppression of force. Pretreatment of PCA with forskolin suppressed histamine-induced force generation but did not abolish [Ca(2+]i rise or MLC phosphorylation. Additionally, forskolin pretreatment reduced filamentous actin in histamine-treated tissues, and prevented histamine-induced changes in the phosphorylation of the actin-regulatory proteins HSP20, VASP, cofilin, and paxillin. Taken together, these results suggest that forskolin-induced complete force suppression is dependent upon the actin cytoskeletal regulation initiated by the phosphorylation changes of the actin regulatory proteins and not on the MLC dephosphorylation. This model of complete force suppression can be employed to further elucidate the mechanisms responsible for smooth muscle tone, and may offer cues to pathological situations, such as hypertension and vasospasm.

  4. Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats

    Science.gov (United States)

    Overton, Donald A.; Stanwood, Gregg D.; Patel, Bhavesh N.; Pragada, Sreenivasa R.; Gordon, M. Kathleen

    2009-01-01

    Rationale Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination. Objectives Compare three methods for determining the threshold dosage for phenobarbital (D) versus no drug (N) DD. Methods Rats learned a D versus N DD in 2-lever operant training chambers. A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed. Three criterion rules were employed, all based on average percent drug lever responses during initial links of the last 6 D and 6 N sessions of a block. The criteria were: D%>66 and N%50 and N%33. Two squads of rats were trained, one immediately after the other. Results All rats discriminated drug versus no drug. In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance. The lowest discriminated dosage significantly differed under the three criterion rules. The squad that was trained 2nd may have benefited by partially duplicating the lever choices of the previous squad. Conclusions The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed, and is higher than the absolute threshold at which discrimination entirely disappears. Threshold estimations closer to absolute threshold can be obtained when criteria are employed that are permissive, and that allow rats to maintain lever preferences. PMID:19082992

  5. Discussion of dosimetric dependencies of experimental light-induced melatonin suppression studies; Diskussion dosimetrischer Aspekte bei experimentellen Studien zur lichtinduzierten Melatoninreduktion

    Energy Technology Data Exchange (ETDEWEB)

    Weber, M.; Schulmeister, K. [ARC Seibersdorf Research (Austria). Akkreditierte Pruefstelle fuer Laser und Optische Strahlung

    2004-07-01

    Based on a literature review, dosimetric dependencies of light-induced melatonin suppression are discussed. The quantity of light used to suppress melatonin in study trials is often given in terms of illuminance at the cornea, as this is easy to measure. The use of the term illuminance for such studies is critically discussed. A more appropriate measure would be effective irradiance. In our work we present a simplified model to estimate the photobiological effective irradiance and the spot size of the retinal image. Important issues which should ideally be considered in melatonin suppression study trials are pointed out. Another aim of this work is to derive from the literature data, up to what time frame the dosedependent relationship between time and melatonin suppression is valid. An evaluation is made of the situation on the workplace with regard to light-induced melatonin suppression. (orig.)

  6. Nardilysin controls intestinal tumorigenesis through HDAC1/p53-dependent transcriptional regulation.

    Science.gov (United States)

    Kanda, Keitaro; Sakamoto, Jiro; Matsumoto, Yoshihide; Ikuta, Kozo; Goto, Norihiro; Morita, Yusuke; Ohno, Mikiko; Nishi, Kiyoto; Eto, Koji; Kimura, Yuto; Nakanishi, Yuki; Ikegami, Kanako; Yoshikawa, Takaaki; Fukuda, Akihisa; Kawada, Kenji; Sakai, Yoshiharu; Ito, Akihiro; Yoshida, Minoru; Kimura, Takeshi; Chiba, Tsutomu; Nishi, Eiichiro; Seno, Hiroshi

    2018-04-19

    Colon cancer is a complex disease affected by a combination of genetic and epigenetic factors. Here we demonstrate that nardilysin (N-arginine dibasic convertase; NRDC), a metalloendopeptidase of the M16 family, regulates intestinal tumorigenesis via its nuclear functions. NRDC is highly expressed in human colorectal cancers. Deletion of the Nrdc gene in ApcMin mice crucially suppressed intestinal tumor development. In ApcMin mice, epithelial cell-specific deletion of Nrdc recapitulated the tumor suppression observed in Nrdc-null mice. Moreover, epithelial cell-specific overexpression of Nrdc significantly enhanced tumor formation in ApcMin mice. Notably, epithelial NRDC controlled cell apoptosis in a gene dosage-dependent manner. In human colon cancer cells, nuclear NRDC directly associated with HDAC1, and controlled both acetylation and stabilization of p53, with alterations of p53 target apoptotic factors. These findings demonstrate that NRDC is critically involved in intestinal tumorigenesis through its epigenetic regulatory function, and targeting NRDC may lead to a novel prevention or therapeutic strategy against colon cancer.

  7. Deconstructing continuous flash suppression

    OpenAIRE

    Yang, Eunice; Blake, Randolph

    2012-01-01

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

  8. [Pharmaceutical advice concerning different pharmaceutical dosage forms].

    Science.gov (United States)

    Szakonyi, Gergely; Zelkó, Romána

    2010-01-01

    The present paper summarizes the commonly applied types of drug uptake and the pharmacists' advice concerning a certain dosage form. The manuscript also deals with the modified release dosage forms and their abbreviations in the name of the marketing authorized products.

  9. [Value of desmopressin stimulation test and high dose dexamethasone suppression testin the etiologic diagnosis of ACTH dependent Cushing's syndrome].

    Science.gov (United States)

    Zhang, Weiwei; Yu, Yerong; Tan, Huiwen; Wang, Chun; Li, Jianwei; An, Zhenmei; Liu, Yuping

    2016-03-22

    To investigate the value of desmopressin (DDAVP) stimulation test and high dose dexamethasone suppression test (HDDST) in establishing the cause of ACTH dependent Cushing's syndrome. The clinical data of patients with ACTH dependent Cushing's syndrome at West China Hospital from January 1, 2010 to September 30, 2015 was analyzed. The sensitivity and specificity of DDAVP stimulation test, HDDST, and the diagnostic accordance rate when the two tests were combined, were evaluated based on the diagnostic gold standard. A total of 85 patients with Cushing's disease and 10 patients with ectopic ACTH syndrome were included. The sensitivity and specificity of DDAVP stimulation test were 87% and 5/5, respectively, whereas those of HDDST were 79% and 8/10, respectively. The standard high dose dexamethasone suppression test showed a higher sensitivity than overnight 8 mg dexamethasone suppression test. When the two tests had consistent results, the diagnostic accordance rate was 100%. DDAVP stimulation test and HDDST are both efficient modalities for the diagnosis of Cushing's Disease and ectopic ACTH syndrome. The accuracy of diagnosis can be further improved by combining the two tests.

  10. Low starting dosage of infliximab with possible escalating dosage in psoriatic arthritis gives the same treatment results as standard dosage of adalimumab or etanercept: results from the nationwide Icelandic ICEBIO registry

    Directory of Open Access Journals (Sweden)

    Gudbjornsson B

    2018-05-01

    Full Text Available Bjorn Gudbjornsson,1,2 Arni Jon Geirsson,3,4 Niels Steen Krogh5 1Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Department of Rheumatology, University Hospital, Reykjavik, Iceland; 4Laeknasetrid - Medical Clinic, University of Iceland, Reykjavik, Iceland; 5Zitelab Aps, Copenhagen, Denmark Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA. Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab <4 mg/kg; infliximab >4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit. The Kruskal–Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. Results: One hundred and eighty-five patients (61% female were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP, numbers of swollen or tender joints, or Disease Activity Score (DAS 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment. Keywords: psoriatic arthritis, outcome, biological treatment, routine care, clinical nationwide registry

  11. Intelligent system for improving dosage control

    Directory of Open Access Journals (Sweden)

    Fabio Cosme Rodrigues dos Santos

    2017-02-01

    Full Text Available Coagulation is one of the most important processes in a drinking-water treatment plant, and it is applied to destabilize impurities in water for the subsequent flocculation stage. Several techniques are currently used in the water industry to determine the best dosage of the coagulant, such as the jar-test method, zeta potential measurements, artificial intelligence methods, comprising neural networks, fuzzy and expert systems, and the combination of the above-mentioned techniques to help operators and engineers in the water treatment process. Current paper presents an artificial neural network approach to evaluate optimum coagulant dosage for various scenarios in raw water quality, using parameters such as raw water color, raw water turbidity, clarified and filtered water turbidity and a calculated Dose Rate to provide the best performance in the filtration process. Another feature in current approach is the use of a backpropagation neural network method to estimate the best coagulant dosage simultaneously at two points of the water treatment plant. Simulation results were compared to the current dosage rate and showed that the proposed system may reduce costs of raw material in water treatment plant.

  12. Stimulus-dependent suppression of chaos in recurrent neural networks

    International Nuclear Information System (INIS)

    Rajan, Kanaka; Abbott, L. F.; Sompolinsky, Haim

    2010-01-01

    Neuronal activity arises from an interaction between ongoing firing generated spontaneously by neural circuits and responses driven by external stimuli. Using mean-field analysis, we ask how a neural network that intrinsically generates chaotic patterns of activity can remain sensitive to extrinsic input. We find that inputs not only drive network responses, but they also actively suppress ongoing activity, ultimately leading to a phase transition in which chaos is completely eliminated. The critical input intensity at the phase transition is a nonmonotonic function of stimulus frequency, revealing a 'resonant' frequency at which the input is most effective at suppressing chaos even though the power spectrum of the spontaneous activity peaks at zero and falls exponentially. A prediction of our analysis is that the variance of neural responses should be most strongly suppressed at frequencies matching the range over which many sensory systems operate.

  13. The Effect of Dosage, Gestational Age and Splenectomy on Anti-IgM Interception of Prenatal B-cell Development in Sheep

    Directory of Open Access Journals (Sweden)

    P. McCullagh

    2003-01-01

    Full Text Available The administration of a single bolus of anti-IgM antibody to foetal lambs early in pregnancy produces prolonged B-cell depletion. The present study investigated this depletion by examining the effect, on B-cell development in the ileal Peyer's patches, of varying the timing and dosage of antibody administration and by supplementing anti-IgM with surgical splenectomy. The capacity of a 1 mg bolus of anti-IgM to deplete Peyer's patches of B cells was lost if its administration was deferred until two thirds of the way through pregnancy, but persisted beyond this time if weight-adjusted doses were used. Splenectomy of the foetus performed at an earlier age failed to extend the age at which a 1 mg dose of antibody remained effective. As the concentration of murine immunoglobulin in foetal serum was greatly reduced after 21 days, it is inferred that ongoing suppression of B-cell development is not dependent on the continued presence of murine immunoglobulin. The enduring nature of suppression could be attributable to a limited period during which differentiation of B cells from stem cells normally occurs, although further studies will be needed to investigate this and other possible explanations for the effect of anti-IgM treatment on prenatal B-cell development in sheep.

  14. Evaluation of students' knowledge about paediatric dosage calculations.

    Science.gov (United States)

    Özyazıcıoğlu, Nurcan; Aydın, Ayla İrem; Sürenler, Semra; Çinar, Hava Gökdere; Yılmaz, Dilek; Arkan, Burcu; Tunç, Gülseren Çıtak

    2018-01-01

    Medication errors are common and may jeopardize the patient safety. As paediatric dosages are calculated based on the child's age and weight, risk of error in dosage calculations is increasing. In paediatric patients, overdose drug prescribed regardless of the child's weight, age and clinical picture may lead to excessive toxicity and mortalities while low doses may delay the treatment. This study was carried out to evaluate the knowledge of nursing students about paediatric dosage calculations. This research, which is of retrospective type, covers a population consisting of all the 3rd grade students at the bachelor's degree in May, 2015 (148 students). Drug dose calculation questions in exam papers including 3 open ended questions on dosage calculation problems, addressing 5 variables were distributed to the students and their responses were evaluated by the researchers. In the evaluation of the data, figures and percentage distribution were calculated and Spearman correlation analysis was applied. Exam question on the dosage calculation based on child's age, which is the most common method in paediatrics, and which ensures right dosages and drug dilution was answered correctly by 87.1% of the students while 9.5% answered it wrong and 3.4% left it blank. 69.6% of the students was successful in finding the safe dose range, and 79.1% in finding the right ratio/proportion. 65.5% of the answers with regard to Ml/dzy calculation were correct. Moreover, student's four operation skills were assessed and 68.2% of the students were determined to have found the correct answer. When the relation among the questions on medication was examined, a significant relation (correlation) was determined between them. It is seen that in dosage calculations, the students failed mostly in calculating ml/dzy (decimal). This result means that as dosage calculations are based on decimal values, calculations may be ten times erroneous when the decimal point is placed wrongly. Moreover, it

  15. Maintenance of Xist Imprinting Depends on Chromatin Condensation State and Rnf12 Dosage in Mice.

    Directory of Open Access Journals (Sweden)

    Atsushi Fukuda

    2016-10-01

    Full Text Available In female mammals, activation of Xist (X-inactive specific transcript is essential for establishment of X chromosome inactivation. During early embryonic development in mice, paternal Xist is preferentially expressed whereas maternal Xist (Xm-Xist is silenced. Unlike autosomal imprinted genes, Xist imprinting for Xm-Xist silencing was erased in cloned or parthenogenetic but not fertilized embryos. However, the molecular mechanism underlying the variable nature of Xm-Xist imprinting is poorly understood. Here, we revealed that Xm-Xist silencing depends on chromatin condensation states at the Xist/Tsix genomic region and on Rnf12 expression levels. In early preimplantation, chromatin decondensation via H3K9me3 loss and histone acetylation gain caused Xm-Xist derepression irrespective of embryo type. Although the presence of the paternal genome during pronuclear formation impeded Xm-Xist derepression, Xm-Xist was robustly derepressed when the maternal genome was decondensed before fertilization. Once Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued XmXpΔ lethality, indicating that loss of Xm-Xist imprinting was irreversible. In late preimplantation, Oct4 served as a chromatin opener to create transcriptional permissive states at Xm-Xist/Tsix genomic loci. In parthenogenetic embryos, Rnf12 overdose caused Xm-Xist derepression via Xm-Tsix repression; physiological Rnf12 levels were essential for Xm-Xist silencing maintenance in fertilized embryos. Thus, chromatin condensation and fine-tuning of Rnf12 dosage were crucial for Xist imprint maintenance by silencing Xm-Xist.

  16. Advances in solid dosage form manufacturing technology.

    Science.gov (United States)

    Andrews, Gavin P

    2007-12-15

    Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation.

  17. Dosage sensitivity shapes the evolution of copy-number varied regions.

    Directory of Open Access Journals (Sweden)

    Benjamin Schuster-Böckler

    2010-03-01

    Full Text Available Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation.

  18. Boxing and mixed martial arts: preliminary traumatic neuromechanical injury risk analyses from laboratory impact dosage data.

    Science.gov (United States)

    Bartsch, Adam J; Benzel, Edward C; Miele, Vincent J; Morr, Douglas R; Prakash, Vikas

    2012-05-01

    In spite of ample literature pointing to rotational and combined impact dosage being key contributors to head and neck injury, boxing and mixed martial arts (MMA) padding is still designed to primarily reduce cranium linear acceleration. The objects of this study were to quantify preliminary linear and rotational head impact dosage for selected boxing and MMA padding in response to hook punches; compute theoretical skull, brain, and neck injury risk metrics; and statistically compare the protective effect of various glove and head padding conditions. An instrumented Hybrid III 50th percentile anthropomorphic test device (ATD) was struck in 54 pendulum impacts replicating hook punches at low (27-29 J) and high (54-58 J) energy. Five padding combinations were examined: unpadded (control), MMA glove-unpadded head, boxing glove-unpadded head, unpadded pendulum-boxing headgear, and boxing glove-boxing headgear. A total of 17 injury risk parameters were measured or calculated. All padding conditions reduced linear impact dosage. Other parameters significantly decreased, significantly increased, or were unaffected depending on padding condition. Of real-world conditions (MMA glove-bare head, boxing glove-bare head, and boxing glove-headgear), the boxing glove-headgear condition showed the most meaningful reduction in most of the parameters. In equivalent impacts, the MMA glove-bare head condition induced higher rotational dosage than the boxing glove-bare head condition. Finite element analysis indicated a risk of brain strain injury in spite of significant reduction of linear impact dosage. In the replicated hook punch impacts, all padding conditions reduced linear but not rotational impact dosage. Head and neck dosage theoretically accumulates fastest in MMA and boxing bouts without use of protective headgear. The boxing glove-headgear condition provided the best overall reduction in impact dosage. More work is needed to develop improved protective padding to minimize

  19. Cell-mediated immune suppression effect of rocket kerosene through dermal exposure in mice

    Directory of Open Access Journals (Sweden)

    Bing-xin XU

    2015-10-01

    Full Text Available Objective To study the effect of cell-mediated immune suppression effect of rocket kerosene (RK through dermal application in mice. Methods Skin delayed type hypersensitivity (DTH was used to observe the relation of the RK amount the skin exposed and the cellular immune inhibitory function. Different amount of the undiluted fuel was smeared directly onto the dorsal skin of mice. Mice in negative and positive control groups were treated with acetone. After the last exposure, all the mice except those in negative control group were allergized by evenly smearing with 1% dinitrofluorobenzene (DNFB solution on their dorsum. Five days after allergy, 1% DNFB solution was smeared onto right ear of all mice to stimulate the allergic reaction. Twenty-four hours after attack, the auricle swelling, spleen index and thymus index in corresponding mice were determined. In the first series of experiments, different dosages of RK were applied once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 1ml/kg.BW×1 and 2ml/kg.BW×1 group. In the second series of experiments, the certain and same dosage of RK was applied for different times, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 0.5mL/kg.BW×2, 0.5ml/kg.BW×3, 0.5ml/kg.BW×4 and 0.5mL/kg.BW×5 group. In the third series of experiments, the different dosages of RK were applied more than once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×5, 1ml/kg.BW×5 and 2ml/kg.BW×5 group. Lymphocyte proliferation experiment in vitrowas conducted to observe the persistent time of the cell-mediated immune suppression in mice by RK dermal exposure. The lymphocyte proliferation induced by concanavalin A (Con A was analyzed by MTT assay, and T lymphocyte subsets (CD3+, CD4+ and CD

  20. Effect of Injection Minimal Dosages of Depot Medroxyprogesterone acetate (DMPA to Body Weight and Blood Chemistry Male Rat Strain Sprague-Dawley

    Directory of Open Access Journals (Sweden)

    Nukman Moeloek

    2009-11-01

    Full Text Available Many family planning program focus more on men. Until now, vasectomy has been the commonly used method for male contraception. However, this method creates inconvenience such as irreversibility and psychological problems. One of the alternatives contraception is the combination of depot medroxyprogesterone acetate (DMPA and androgen. The minimum dosage of DMPA could suppress testosterone level that leads to reduced spermatogenesis and sperm viability. Nevertheless, until now it is not known whether minimum dosages of DMPA have an effect to body weight and blood chemistry. Therefore, this research aimed at determinate the effect of minimal dosages of DMPA to body mass and blood chemistry using male rats (Rattus norvegicus L. strain Sprague-Dawley as model. This research using completely randomized design, unequal size sample, castration treatments and several doses DMPA (1.25, 0.625, and 0.313 milligram. Injecting of DMPA conducted intramuscularly on week 0 and week 12. Normality/homogeneity Data normality were analyzed before ANOVA test. Then, abnormal data were tested using Kruskal-Wallis test. The result shows that injection of DMPA in various doses do not have an effect on body weight and blood chemistry such as erytrocytes, haemoglobin, hematocrite, HDL, LDL, total cholesterol, SGOT, SGPT and triglyseride (p>0,05. Furthermore, it is concluded that that no effect of minimal dosages of DMPA to body mass and blood chemistry of rat.

  1. Flunarizine suppresses endothelial Angiopoietin-2 in a calcium - dependent fashion in sepsis.

    Science.gov (United States)

    Retzlaff, Jennifer; Thamm, Kristina; Ghosh, Chandra C; Ziegler, Wolfgang; Haller, Hermann; Parikh, Samir M; David, Sascha

    2017-03-09

    Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection leading to systemic inflammation and endothelial barrier breakdown. The vascular-destabilizing factor Angiopoietin-2 (Angpt-2) has been implicated in these processes in humans. Here we screened in an unbiased approach FDA-approved compounds with respect to Angpt-2 suppression in endothelial cells (ECs) in vitro. We identified Flunarizine - a well-known anti-migraine calcium channel (CC) blocker - being able to diminish intracellular Angpt-2 protein in a time- and dose-dependent fashion thereby indirectly reducing the released protein. Moreover, Flunarizine protected ECs from TNFα-induced increase in Angpt-2 transcription and vascular barrier breakdown. Mechanistically, we could exclude canonical Tie2 signalling being responsible but found that three structurally distinct T-type - but not L-type - CC blockers can suppress Angpt-2. Most importantly, experimental increase in intracellular calcium abolished Flunarizine's effect. Flunarizine was also able to block the injurious increase of Angpt-2 in murine endotoxemia in vivo. This resulted in reduced pulmonary adhesion molecule expression (intercellular adhesion molecule-1) and tissue infiltration of inflammatory cells (Gr-1). Our finding could have therapeutic implications as side effects of Flunarizine are low and specific sepsis therapeutics that target the dysregulated host response are highly desirable.

  2. Microbial quality of some herbal solid dosage forms

    African Journals Online (AJOL)

    STORAGESEVER

    2010-03-15

    Mar 15, 2010 ... Key words: Microbial quality, herbal, contamination, solid dosage form ... The type of dosage form, packaging, manufacturing and expiration dates of subject solid herbal .... According to WHO report (2002), Salmonella food.

  3. Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Pauline E Jullien

    2010-03-01

    Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

  4. Transverse momentum and centrality dependence of high-ptnon-photonic electron suppression in Au+Au collisions at $\\sqrt{s_{NN}}$= 200 GeV

    Energy Technology Data Exchange (ETDEWEB)

    Abelev, B.I.; Adams, J.; Aggarwal, M.M.; Ahammed, Z.; Amonett,J.; Anderson, B.D.; Anderson, M.; Arkhipkin, D.; Averichev, G.S.; Bai,Y.; Balewski, J.; Barannikova, O.; Barnby, L.S.; Baudot, J.; Bekele, S.; Belaga, V.V.; Bellingeri-Laurikainen, A.; Bellwied, R.; Benedosso, F.; Bhardwaj, S.; Bhasin, A.; Bhati, A.K.; Bichsel, H.; Bielcik, J.; Bielcikova, J.; Bland, L.C.; Blyth, S.-L.; Bonner, B.E.; Botje, M.; Bouchet, J.; Brandin, A.V.; Bravar, A.; Bystersky, M.; Cadman, R.V.; Cai,X.Z.; Caines, H.; Calderon de la Barca Sanchez, M.; Castillo, J.; Catu,O.; Cebra, D.; Chajecki, Z.; Chaloupka, P.; Chattopadhyay, S.; Chen,H.F.; Chen, J.H.; Cheng, J.; Cherney, M.; Chikanian, A.; Christie, W.; Coffin, J.P.; Cormier, T.M.; Cosentino, M.R.; Cramer, J.G.; Crawford,H.J.; Das, D.; Das, S.; Daugherity, M.; de Moura, M.M.; Dedovich, T.G.; DePhillips, M.; Derevschikov, A.A.; Didenko, L.; Dietel, T.; Djawotho,P.; Dogra, S.M.; Dong, W.J.; Dong, X.; Draper, J.E.; Du, F.; Dunin, V.B.; Dunlop, J.C.; Dutta Mazumdar, M.R.; Eckardt, V.; Edwards, W.R.; Efimov,L.G.; Emelianov, V.; Engelage, J.; Eppley, G.; Erazmus, B.; Estienne, M.; Fachini, P.; Fatemi, R.; Fedorisin, J.; Filimonov, K.; Filip, P.; Finch,E.; Fine, V.; Fisyak, Y.; Fu, J.; Gagliardi, C.A.; Gaillard, L.; Ganti,M.S.; Ghazikhanian, V.; Ghosh, P.; Gonzalez, J.S.; Gorbunov, Y.G.; Gos,H.; Grebenyuk, O.; Grosnick, D.; Guertin, S.M.; Guimaraes, K.S.F.F.; Guo,Y.; Gupta, N.; Gutierrez, T.D.; Haag, B.; Hallman, T.J.; Hamed, A.; Harris, J.W.; He, W.; Heinz, M.; Henry, T.W.; Hepplemann, S.; Hippolyte,B.; Hirsch, A.; Hjort, E.; Hoffman, A.M.; Hoffmann, G.W.; Horner, M.J.; Huang, H.Z.; Huang, S.L.; Hughes, E.W.; Humanic, T.J.; Igo, G.; Jacobs,P.; Jacobs, W.W.; Jakl, P.; Jia, F.; Jiang, H.; Jones, P.G.; Judd, E.G.; Kabana, S.; Kang, K.; Kapitan, J.; Kaplan, M.; Keane, D.; Kechechyan, A.; Khodyrev, V.Yu.; Kim, B.C.; Kiryluk, J.; Kisiel, A.; Kislov, E.M.; Klein,S.R.; Kocoloski, A.; Koetke, D.D.; et al.

    2006-07-11

    The STAR collaboration at RHIC reports measurements of theinclusive yield of non-photonic electrons, which arise dominantly fromsemi-leptonic decays of heavy flavor mesons, over a broad range oftransverse momenta (1.2suppression in central AuAu collisions athigh pt, suggesting substantial heavy quark energy loss at RHIC. Thecentrality and \\pt dependences of the suppression provide constraints ontheoretical models of suppression.

  5. Suppression of matrix protein synthesis in endothelial cells by herpes simplex virus is not dependent on viral protein synthesis

    International Nuclear Information System (INIS)

    Kefalides, N.A.

    1986-01-01

    The synthesis of matrix proteins by human endothelial cells (EC) in vitro was studied before and at various times after infection with Herpes Simplex virus Type 1 (HSV-1) or 2 (HSV-2). Monolayers of EC were either mock-infected or infected with virus for 1 hr at a multiplicity infection (MOI) of 5 to 20 at 37 0 C. Control and infected cultures were pulse-labeled for 1 or 2 hrs with either [ 14 C]proline or [ 35 S]methionine. Synthesis of labeled matrix proteins was determined by SDS-gel electrophoresis. Suppression of synthesis of fibronectin, Type IV collagen and thrombospondin began as early as 2 hrs and became almost complete by 10 hrs post-infection. The degree of suppression varied with the protein and the virus dose. Suppression of Type IV collagen occurred first followed by that of fibronectin and then thrombospondin. Infection of EC with UV irradiated HSV-1 or HSV-2 resulted in suppression of host-cell protein synthesis as well as viral protein synthesis. Infection with intact virus in the presence of actinomycin-D resulted in suppression of both host-cell and viral protein synthesis. The data indicate that infection of EC with HSV leads to suppression of matrix protein synthesis which does not depend on viral protein synthesis

  6. Dependence of J/ψ suppression in heavy ion collisions on total transverse energy, nucleon numbers and J/ψ transverse momentum

    International Nuclear Information System (INIS)

    Ftacnik, J.; Lichard, P.

    1989-01-01

    We present a set of semiquantitative predictions for the behaviour of J/ψ suppression in heavy ion collisions as a function of the total transverse energy, nucleon numbers of colliding ions and the J/ψ transverse momentum. These predictions are based on the assumption that all of J/ψ suppression is due to J/ψ and χ disintegrations in collisions with hadrons in a dense hadronic gas formed in the heavy ion collisions. The hydrodynamic evolution of the hadron gas is taken into account. The onset of the quark-gluon plasma formation should manifest itself by clear qualitative deviations from J/ψ suppression calculated in this way, in particular as thresholds or kinks in the E T -dependence, or as a threshold for J/ψ suppression as a function of the atomic number of the target, expected at Cu or below. (orig.)

  7. 21 CFR 520.905 - Fenbendazole oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms. ...

  8. Buccal Dosage Forms: General Considerations for Pediatric Patients.

    Science.gov (United States)

    Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

    2017-02-01

    The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

  9. Switch between life history strategies due to changes in glycolytic enzyme gene dosage in Saccharomyces cerevisiae.

    Science.gov (United States)

    Wang, Shaoxiao; Spor, Aymé; Nidelet, Thibault; Montalent, Pierre; Dillmann, Christine; de Vienne, Dominique; Sicard, Delphine

    2011-01-01

    Adaptation is the process whereby a population or species becomes better fitted to its habitat through modifications of various life history traits which can be positively or negatively correlated. The molecular factors underlying these covariations remain to be elucidated. Using Saccharomyces cerevisiae as a model system, we have investigated the effects on life history traits of varying the dosage of genes involved in the transformation of resources into energy. Changing gene dosage for each of three glycolytic enzyme genes (hexokinase 2, phosphoglucose isomerase, and fructose-1,6-bisphosphate aldolase) resulted in variation in enzyme activities, glucose consumption rate, and life history traits (growth rate, carrying capacity, and cell size). However, the range of effects depended on which enzyme was expressed differently. Most interestingly, these changes revealed a genetic trade-off between carrying capacity and cell size, supporting the discovery of two extreme life history strategies already described in yeast populations: the "ants," which have lower glycolytic gene dosage, take up glucose slowly, and have a small cell size but reach a high carrying capacity, and the "grasshoppers," which have higher glycolytic gene dosage, consume glucose more rapidly, and allocate it to a larger cell size but reach a lower carrying capacity. These results demonstrate antagonist pleiotropy for glycolytic genes and show that altered dosage of a single gene drives a switch between two life history strategies in yeast.

  10. Intercavitary implants dosage calculation

    International Nuclear Information System (INIS)

    Rehder, B.P.

    The use of spacial geometry peculiar to each treatment for the attainment of intercavitary and intersticial implants dosage calculation is presented. The study is made in patients with intercavitary implants by applying a modified Manchester technique [pt

  11. 21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms. ...

  12. Radiation dosage

    Energy Technology Data Exchange (ETDEWEB)

    Finston, Roland [Health Physics, Stanford University, Stanford, CA (United States)

    1986-07-01

    Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative.

  13. Radiation dosage

    International Nuclear Information System (INIS)

    Finston, Roland

    1986-01-01

    Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative

  14. Comprehensive review on additives of topical dosage forms for drug delivery.

    Science.gov (United States)

    Garg, Tarun; Rath, Goutam; Goyal, Amit K

    2015-12-01

    Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

  15. Radiation dosage of various CT-methods in lung diagnostics

    International Nuclear Information System (INIS)

    Heinz-Peer, G.; Weninger, F.; Nowotny, R.; Herold, C.J.

    1996-01-01

    Introduction of the computed tomography index CTDI and the multiple scan average dose (MSAD) has led to standardization of the dose description in CT examinations. Despite the use of these dose parameters, many different dosages are reported in the literature for different CT methods. In addition, there is still a wide range of radiation dosimetry results reported for conventional CT, helical CT, and HRCT used in chest examinations. The variations in dosage are mainly due to difference in factors affecting the dose, i.e. beam geometry, beam quality, scanner geometry ('generation'), and operating parameters. In addition, CT dosimetry instrumentation and methodology make a contribution to dosages. Recent studies calculating differences in factors affecting dosage and CT dosimetry and using similar operating parameters, show similar results in CT dosimetry for conventional and helical CT. On the other hand, dosages for HRCT were greatly reduced. This was mainly caused by narrow beam collimation and increasing section spacing. (orig.) [de

  16. Hydraulic Modular Dosaging Systems for Machine Drives

    Directory of Open Access Journals (Sweden)

    A. J. Kotlobai

    2005-01-01

    Full Text Available The justified principle of making modular dosaging systems for positive-displacement multimotor hydraulic drives used in running gear and technological equipment of mobile construction, road and agricultural machines makes it possible to synchronize motion of running parts. The examples of the realization of modular dosaging systems and an algorithm of their operation are given in the paper.

  17. Tissue- and stage-dependent dosage compensation on the Neo-X chromosome in drosophila pseudoobscura

    KAUST Repository

    Nozawa, Masafumi

    2013-12-03

    Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly not homologous, and the average gene expression level on these chromosomes may not be the same even under DC, which complicates comparisons between chromosomes. Many genes with sex-biased expression also make comparisons between sexes difficult. To overcome these issues, we investigated DC by comparing the expression of neo-X-linked genes in Drosophila pseudoobscura with those of their autosomal orthologs in other Drosophila species. The ratio of the former to the latter in males would be 1 under DC, whereas it becomes 0.5 without DC. We found that the ratio was ∼0.85 for adult whole bodies, indicating that the DC is incomplete on the neo-X chromosome in adults as a whole. The ratio (∼0.90) was also significantly less than 1 for adult bodies without gonads, whereas it was ∼1.0 for adult heads. These results indicate that DC varies among tissues. Our sliding-window analysis of the ratio also revealed that the upregulation of neo-X-linked genes in males occurred chromosome wide in all tissues analyzed, indicating global upregulation mechanisms. However, we found that gene functions also affected the levels of DC. Furthermore, most of the genes recently moved to the X were already under DC at the larval stage but not at the adult stage. These results suggest that DC in Drosophila species operates in a tissue/stage-dependent manner. © 2013 The Author 2013. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.

  18. Safety of higher dosages of Viscum album L. in animals and humans - systematic review of immune changes and safety parameters

    Directory of Open Access Journals (Sweden)

    Kiene Helmut

    2011-08-01

    Full Text Available Abstract Background Viscum album L extracts (VAE, mistletoe and isolated mistletoe lectins (ML have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects. Methods Systematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg and assessing immune parameters or infections or adverse drug reactions. Results 69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, Viscum album was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 μg/kg in humans and in animals up to 14 μg/kg subcutaneously, 50 μg/kg nasally and 500 μg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS, fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases. Conclusions Application of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages.

  19. Chromosome VIII disomy influences the nonsense suppression efficiency and transition metal tolerance of the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Zadorsky, S P; Sopova, Y V; Andreichuk, D Y; Startsev, V A; Medvedeva, V P; Inge-Vechtomov, S G

    2015-06-01

    The SUP35 gene of the yeast Saccharomyces cerevisiae encodes the translation termination factor eRF3. Mutations in this gene lead to the suppression of nonsense mutations and a number of other pleiotropic phenotypes, one of which is impaired chromosome segregation during cell division. Similar effects result from replacing the S. cerevisiae SUP35 gene with its orthologues. A number of genetic and epigenetic changes that occur in the sup35 background result in partial compensation for this suppressor effect. In this study we showed that in S. cerevisiae strains in which the SUP35 orthologue from the yeast Pichia methanolica replaces the S. cerevisiae SUP35 gene, chromosome VIII disomy results in decreased efficiency of nonsense suppression. This antisuppressor effect is not associated with decreased stop codon read-through. We identified SBP1, a gene that localizes to chromosome VIII, as a dosage-dependent antisuppressor that strongly contributes to the overall antisuppressor effect of chromosome VIII disomy. Disomy of chromosome VIII also leads to a change in the yeast strains' tolerance of a number of transition metal salts. Copyright © 2015 John Wiley & Sons, Ltd.

  20. T cell suppression by naturally occurring HLA-G-expressing regulatory CD4+ T cells is IL-10-dependent and reversible.

    Science.gov (United States)

    Huang, Yu-Hwa; Zozulya, Alla L; Weidenfeller, Christian; Schwab, Nicholas; Wiendl, Heinz

    2009-08-01

    CD4(+) T cells constitutively expressing the immune-tolerogenic HLA-G have been described recently as a new type of nT(reg) (HLA-G(pos) T(reg)) in humans. HLA-G(pos) T(reg) accumulate at sites of inflammation and are potent suppressors of T cell proliferation in vitro, suggesting their role in immune regulation. We here characterize the mechanism of how CD4(+) HLA-G(pos) T(reg) influence autologous HLA-G(neg) T(resp) function. Using a suppression system free of APC, we demonstrate a T-T cell interaction, resulting in suppression of HLA-G(neg) T(resp), which is facilitated by TCR engagement on HLA-G(pos) T(reg). Suppression is independent of cell-cell contact and is reversible, as the removal of HLA-G(pos) T(reg) from the established coculture restored the proliferative capability of responder cells. Further, HLA-G(pos) T(reg)-mediated suppression critically depends on the secretion of IL-10 but not TGF-beta.

  1. 21 CFR 526.1696 - Penicillin intramammary dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin...

  2. Andrographolide suppresses TRIF-dependent signaling of toll-like receptors by targeting TBK1.

    Science.gov (United States)

    Kim, Ah-Yeon; Shim, Hyun-Jin; Shin, Hyeon-Myeong; Lee, Yoo Jung; Nam, Hyeonjeong; Kim, Su Yeon; Youn, Hyung-Sun

    2018-04-01

    Toll-like receptors (TLRs) play a crucial role in danger recognition and induction of innate immune response against bacterial and viral infections. The TLR adaptor molecule, toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF), facilitates TLR3 and TLR4 signaling, leading to the activation of the transcription factor, NF-κB and interferon regulatory factor 3 (IRF3). Andrographolide, the active component of Andrographis paniculata, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the role of andrographolide in TLR signaling pathways. Andrographolide suppressed NF-κB activation as well as COX-2 expression induced by TLR3 or TLR4 agonists. Andrographolide also suppressed the activation of IRF3 and the expression of interferon inducible protein-10 (IP-10) induced by TLR3 or TLR4 agonists. Andrographolide attenuated ligand-independent activation of IRF3 following overexpression of TRIF, TBK1, or IRF3. Furthermore, andrographolide inhibited TBK1 kinase activity in vitro. These results indicate that andrographolide modulates the TRIF-dependent pathway of TLRs by targeting TBK1 and represents a potential new anti-inflammatory candidate. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma.

    Science.gov (United States)

    Kent, Lindsey N; Bae, Sooin; Tsai, Shih-Yin; Tang, Xing; Srivastava, Arunima; Koivisto, Christopher; Martin, Chelsea K; Ridolfi, Elisa; Miller, Grace C; Zorko, Sarah M; Plevris, Emilia; Hadjiyannis, Yannis; Perez, Miguel; Nolan, Eric; Kladney, Raleigh; Westendorp, Bart; de Bruin, Alain; Fernandez, Soledad; Rosol, Thomas J; Pohar, Kamal S; Pipas, James M; Leone, Gustavo

    2017-03-01

    Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC). Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output, we have shown that copy number gains in E2f1 or E2f3b resulted in dosage-dependent spontaneous HCC in mice without the involvement of additional organs. Conversely, germ-line loss of E2f1 or E2f3b, but not E2f3a, protected mice against HCC. Combinatorial mapping of chromatin occupancy and transcriptome profiling identified an E2F1- and E2F3B-driven transcriptional program that was associated with development and progression of HCC. These findings demonstrate a direct and cell-autonomous role for E2F activators in human cancer.

  4. 21 CFR 520.1696 - Penicillin oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

  5. 21 CFR 520.45 - Albendazole oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

  6. Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition.

    Directory of Open Access Journals (Sweden)

    Kevin Bray

    Full Text Available mTOR inhibitors are used clinically to treat renal cancer but are not curative. Here we show that autophagy is a resistance mechanism of human renal cell carcinoma (RCC cell lines to mTOR inhibitors. RCC cell lines have high basal autophagy that is required for survival to mTOR inhibition. In RCC4 cells, inhibition of mTOR with CCI-779 stimulates autophagy and eliminates RIP kinases (RIPKs and this is blocked by autophagy inhibition, which induces RIPK- and ROS-dependent necroptosis in vitro and suppresses xenograft growth. Autophagy of mitochondria is required for cell survival since mTOR inhibition turns off Nrf2 antioxidant defense. Thus, coordinate mTOR and autophagy inhibition leads to an imbalance between ROS production and defense, causing necroptosis that may enhance cancer treatment efficacy.

  7. Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.

    Science.gov (United States)

    Debotton, Nir; Dahan, Arik

    2017-01-01

    Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products. © 2016 Wiley Periodicals, Inc.

  8. MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon response pathway.

    Science.gov (United States)

    Yang, Chuan He; Wang, Yinan; Sims, Michelle; Cai, Chun; He, Ping; Häcker, Hans; Yue, Junming; Cheng, Jinjun; Boop, Frederick A; Pfeffer, Lawrence M

    2017-12-22

    Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs (miRNAs) play critical roles in regulating the cancer cell phenotype, the underlying mechanisms of how they regulate tumorigenesis are incompletely understood. We previously showed that miR-203a is expressed at relatively low levels in GBM patients, and ectopic miR-203a expression in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by interferon (IFN) or temozolomide in vitro , and inhibited GBM tumorigenesis in vivo . Here we show that ectopic expression of miR-203a in GBM cell lines promotes the IFN response pathway as evidenced by increased IFN production and IFN-stimulated gene (ISG) expression, and high basal tyrosine phosphorylation of multiple STAT proteins. Importantly, we identified that miR-203a directly suppressed the protein levels of ataxia-telangiectasia mutated (ATM) kinase that negatively regulates IFN production. We found that high ATM expression in GBM correlates with poor patient survival and that ATM expression is inversely correlated with miR-203a expression. Knockout of ATM expression and inhibition of ATM function in GBM cell lines inhibited cell proliferation and migration, increased sensitivity to apoptosis induced by therapeutic agents in vitro , and markedly suppressed GBM tumor growth and promoted animal survival. In contrast, restoring ATM levels in GBM cells ectopically expressing miR-203a increased tumorigenicity and decreased animal survival. Our study suggests that low miR-203a expression in GBM suppresses the interferon response through an ATM-dependent pathway.

  9. Forskolin suppresses delayed-rectifier K+ currents and enhances spike frequency-dependent adaptation of sympathetic neurons.

    Science.gov (United States)

    Angel-Chavez, Luis I; Acosta-Gómez, Eduardo I; Morales-Avalos, Mario; Castro, Elena; Cruzblanca, Humberto

    2015-01-01

    In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K+ channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K+ channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV). Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and IKV with an IC50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels.

  10. Transverse momentum and centrality dependence of high-pT nonphotonic electron suppression in Au+Au collisions at sqrt[s NN]=200 GeV.

    Science.gov (United States)

    Abelev, B I; Aggarwal, M M; Ahammed, Z; Anderson, B D; Arkhipkin, D; Averichev, G S; Bai, Y; Balewski, J; Barannikova, O; Barnby, L S; Baudot, J; Baumgart, S; Belaga, V V; Bellingeri-Laurikainen, A; Bellwied, R; Benedosso, F; Betts, R R; Bhardwaj, S; Bhasin, A; Bhati, A K; Bichsel, H; Bielcik, J; Bielcikova, J; Bland, L C; Blyth, S-L; Bombara, M; Bonner, B E; Botje, M; Bouchet, J; Brandin, A V; Bravar, A; Burton, T P; Bystersky, M; Cadman, R V; Cai, X Z; Caines, H; Calderón de la Barca Sánchez, M; Callner, J; Catu, O; Cebra, D; Chajecki, Z; Chaloupka, P; Chattopadhyay, S; Chen, H F; Chen, J H; Chen, J Y; Cheng, J; Cherney, M; Chikanian, A; Christie, W; Chung, S U; Coffin, J P; Cormier, T M; Cosentino, M R; Cramer, J G; Crawford, H J; Das, D; Dash, S; Daugherity, M; de Moura, M M; Dedovich, T G; Dephillips, M; Derevschikov, A A; Didenko, L; Dietel, T; Djawotho, P; Dogra, S M; Dong, X; Drachenberg, J L; Draper, J E; Du, F; Dunin, V B; Dunlop, J C; Dutta Mazumdar, M R; Eckardt, V; Edwards, W R; Efimov, L G; Emelianov, V; Engelage, J; Eppley, G; Erazmus, B; Estienne, M; Fachini, P; Fatemi, R; Fedorisin, J; Feng, A; Filip, P; Finch, E; Fine, V; Fisyak, Y; Fu, J; Gagliardi, C A; Gaillard, L; Ganti, M S; Garcia-Solis, E; Ghazikhanian, V; Ghosh, P; Gorbunov, Y G; Gos, H; Grebenyuk, O; Grosnick, D; Guertin, S M; Guimaraes, K S F F; Gupta, N; Haag, B; Hallman, T J; Hamed, A; Harris, J W; He, W; Heinz, M; Henry, T W; Heppelmann, S; Hippolyte, B; Hirsch, A; Hjort, E; Hoffman, A M; Hoffmann, G W; Hofman, D; Hollis, R; Horner, M J; Huang, H Z; Hughes, E W; Humanic, T J; Igo, G; Iordanova, A; Jacobs, P; Jacobs, W W; Jakl, P; Jia, F; Jones, P G; Judd, E G; Kabana, S; Kang, K; Kapitan, J; Kaplan, M; Keane, D; Kechechyan, A; Kettler, D; Khodyrev, V Yu; Kim, B C; Kiryluk, J; Kisiel, A; Kislov, E M; Klein, S R; Knospe, A G; Kocoloski, A; Koetke, D D; Kollegger, T; Kopytine, M; Kotchenda, L; Kouchpil, V; Kowalik, K L; Kravtsov, P; Kravtsov, V I; Krueger, K; Kuhn, C; Kulikov, A I; Kumar, A; Kurnadi, P; Kuznetsov, A A; Lamont, M A C; Landgraf, J M; Lange, S; Lapointe, S; Laue, F; Lauret, J; Lebedev, A; Lednicky, R; Lee, C-H; Lehocka, S; LeVine, M J; Li, C; Li, Q; Li, Y; Lin, G; Lin, X; Lindenbaum, S J; Lisa, M A; Liu, F; Liu, H; Liu, J; Liu, L; Ljubicic, T; Llope, W J; Longacre, R S; Love, W A; Lu, Y; Ludlam, T; Lynn, D; Ma, G L; Ma, J G; Ma, Y G; Magestro, D; Mahapatra, D P; Majka, R; Mangotra, L K; Manweiler, R; Margetis, S; Markert, C; Martin, L; Matis, H S; Matulenko, Yu A; McClain, C J; McShane, T S; Melnick, Yu; Meschanin, A; Millane, J; Miller, M L; Minaev, N G; Mioduszewski, S; Mironov, C; Mischke, A; Mitchell, J; Mohanty, B; Morozov, D A; Munhoz, M G; Nandi, B K; Nattrass, C; Nayak, T K; Nelson, J M; Nepali, N S; Netrakanti, P K; Nogach, L V; Nurushev, S B; Odyniec, G; Ogawa, A; Okorokov, V; Oldenburg, M; Olson, D; Pachr, M; Pal, S K; Panebratsev, Y; Pavlinov, A I; Pawlak, T; Peitzmann, T; Perevoztchikov, V; Perkins, C; Peryt, W; Phatak, S C; Planinic, M; Pluta, J; Poljak, N; Porile, N; Poskanzer, A M; Potekhin, M; Potrebenikova, E; Potukuchi, B V K S; Prindle, D; Pruneau, C; Putschke, J; Qattan, I A; Raniwala, R; Raniwala, S; Ray, R L; Relyea, D; Ridiger, A; Ritter, H G; Roberts, J B; Rogachevskiy, O V; Romero, J L; Rose, A; Roy, C; Ruan, L; Russcher, M J; Sahoo, R; Sakrejda, I; Sakuma, T; Salur, S; Sandweiss, J; Sarsour, M; Sazhin, P S; Schambach, J; Scharenberg, R P; Schmitz, N; Seger, J; Selyuzhenkov, I; Seyboth, P; Shabetai, A; Shahaliev, E; Shao, M; Sharma, M; Shen, W Q; Shimanskiy, S S; Sichtermann, E P; Simon, F; Singaraju, R N; Smirnov, N; Snellings, R; Sorensen, P; Sowinski, J; Speltz, J; Spinka, H M; Srivastava, B; Stadnik, A; Stanislaus, T D S; Staszak, D; Stock, R; Strikhanov, M; Stringfellow, B; Suaide, A A P; Suarez, M C; Subba, N L; Sumbera, M; Sun, X M; Sun, Z; Surrow, B; Symons, T J M; Szanto de Toledo, A; Takahashi, J; Tang, A H; Tarnowsky, T; Thomas, J H; Timmins, A R; Timoshenko, S; Tokarev, M; Trainor, T A; Trentalange, S; Tribble, R E; Tsai, O D; Ulery, J; Ullrich, T; Underwood, D G; Van Buren, G; van der Kolk, N; van Leeuwen, M; Vander Molen, A M; Varma, R; Vasilevski, I M; Vasiliev, A N; Vernet, R; Vigdor, S E; Viyogi, Y P; Vokal, S; Voloshin, S A; Waggoner, W T; Wang, F; Wang, G; Wang, J S; Wang, X L; Wang, Y; Watson, J W; Webb, J C; Westfall, G D; Wetzler, A; Whitten, C; Wieman, H; Wissink, S W; Witt, R; Wu, J; Wu, Y; Xu, N; Xu, Q H; Xu, Z; Yepes, P; Yoo, I-K; Yue, Q; Yurevich, V I; Zhan, W; Zhang, H; Zhang, W M; Zhang, Y; Zhang, Z P; Zhao, Y; Zhong, C; Zhou, J; Zoulkarneev, R; Zoulkarneeva, Y; Zubarev, A N; Zuo, J X

    2007-05-11

    The STAR collaboration at the BNL Relativistic Heavy-Ion Collider (RHIC) reports measurements of the inclusive yield of nonphotonic electrons, which arise dominantly from semileptonic decays of heavy flavor mesons, over a broad range of transverse momenta (1.2suppression in central Au+Au collisions at high p(T), suggesting substantial heavy-quark energy loss at RHIC. The centrality and p(T) dependences of the suppression provide constraints on theoretical models of suppression.

  11. Suppression of a thymus dependent humoral response in mice by Concanavalin A in vivo

    International Nuclear Information System (INIS)

    Egan, H.S.; Ekstedt, R.D.

    1975-01-01

    Mice treated with Concanavalin A prior to immunization with sheep erthyrocytes exhibit a markedly reduced plaque forming spleen cell response. This immunosuppressive effect could be reversed by using higher doses of antigen or priming the animals with nonimmunizing doses of antigen prior to Concanavalin A injection designed to either by-pass or enhance thymus derived lymphocyte functions. It was also demonstrated that Concanavalin A in vivo activated the thymus derived lymphocyte subpopulation in the spleen, and this activation was dose dependent and correlated with the immunosuppression observed. Animals injected with Concanavalin A at various times prior to whole body lethal irradiation would not support the plaque forming cell response of adoptively transferred normal syngeneic spleen cells. This effect was shown to be time and dose of Concanavalin A dependent. It was also shown that the route of injection of Concanavalin A prior to irradiation determined the results observed, in that the intravenous route resulted in the suppression of transferred cells, while the intraperitoneal route showed no effect. It is suggested that Concanavalin A induced immunosuppression of the humoral, thymus dependent immune response in mice results for the activation of a subpopulation of thymus derived suppressors cells, and that the effect is short lived, radiation resistant, and dose of Concanavalin A and antigen dependent

  12. beta. -Amyloid gene dosage in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Murdoch, G H; Manuelidis, L; Kim, J H; Manuelidis, E E

    1988-01-11

    The 4-5 kd amyloid ..beta..-peptide is a major constituent of the characteristic amyloid plaque of Alzheimer's disease. It has been reported that some cases of sporatic Alzheimer's disease are associated with at least a partial duplication of chromosome 21 containing the gene corresponding to the 695 residue precursor of this peptide. To contribute to an understanding of the frequency to such a duplication event in the overall Alzheimer's population, the authors have determined the gene dosage of the ..beta..-amyloid gene in this collection of cases. All cases had a clinical diagnosis of Alzheimer's confirmed neuropathologically. Each Alzheimer's case had an apparent normal diploid ..beta..-amyloid gene dosage, while control Down's cases had the expected triploid dosage. Thus partial duplication of chromosome 21 may be a rare finding in Alzheimer's disease. Similar conclusions were just reported in several studies of the Harvard Alzheimer collection.

  13. 21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

  14. TGF-β Suppression of HBV RNA through AID-Dependent Recruitment of an RNA Exosome Complex

    Science.gov (United States)

    Kitamura, Kouichi; Wang, Zhe; Chowdhury, Sajeda; Monjurul, Ahasan Md; Wakae, Kousho; Koura, Miki; Shimadu, Miyuki; Kinoshita, Kazuo; Muramatsu, Masamichi

    2015-01-01

    Transforming growth factor (TGF)-β inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-β is dependent on AID expression, which significantly decreases both HBV transcripts and viral DNA, resulting in inhibition of viral replication. Immunoprecipitation reveals that AID physically associates with viral P protein that binds to specific virus RNA sequence called epsilon. AID also binds to an RNA degradation complex (RNA exosome proteins), indicating that AID, RNA exosome, and P protein form an RNP complex. Suppression of HBV transcripts by TGF-β was abrogated by depletion of either AID or RNA exosome components, suggesting that AID and the RNA exosome involve in TGF-β mediated suppression of HBV RNA. Moreover, AID-mediated HBV reduction does not occur when P protein is disrupted or when viral transcription is inhibited. These results suggest that induced expression of AID by TGF-β causes recruitment of the RNA exosome to viral RNP complex and the RNA exosome degrades HBV RNA in a transcription-coupled manner. PMID:25836330

  15. 21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

  16. Investigation of contrast agent dosage for perfusion-weighted MRI

    International Nuclear Information System (INIS)

    Erb, G.; Benner, T.; Heiland, S.; Reith, W.; Sartor, K.; Forsting, M.

    1997-01-01

    Purpose: In this study we investigated, whether increasing the dosage of a paramagnetic contrast agent results in a stronger signal decrease in T 2 *-weighted perfusion sequences and therefore more meaningful parameter maps. Material and methods: In a prospective study bolus injection of gadolinium-DTPA was performed at dosages of 0.1, 0.2, and 0.3 mmol/kg body weight (BW) in 10 patients each. Before, during and after bolus injection 40 T 2 *-weighted images of a reference brain slice were acquired within 65.6 seconds on a 1.0 T clinical scanner and perfusion parameters were calculated. Results: Due to the limited signal decrease during bolus passage and the resulting low signal-difference-to-noise ratio (ΔS/N) no reliable differentiation of gray and white matter was possible at a contrast agent dosage of 0.1 mmol/kg BW. Only at higher dosages, both, signal decrease and ΔS/N were strong enough to allow differentiation of gray and white matter and to yield reliable parameter maps. Conclusion: For meaningful MR perfusion imaging at 1.0 T and with the given sequence a contrast agent dosage of at least 0.2 mmol/kg BW is necessary, if a 0.5-molar contrast agent is used. (orig.) [de

  17. PERIPHERAL IMMUNE SYSTEM SUPPRESSION IN EARLY ABSTINENT ALCOHOL DEPENDENT INDIVIDUALS: LINKS TO STRESS AND CUE-RELATED CRAVING

    Science.gov (United States)

    Fox, Helen C; Milivojevic, Verica; Angarita, Gustavo A; Stowe, Raymond; Sinha, Rajita

    2017-01-01

    Background Peripheral immune system cytokines may play an integral role in underlying sensitized stress response and alcohol craving during early withdrawal. To date, the nature of these immune changes during early abstinence have not been examined. Methods Thirty-nine early abstinent, treatment-seeking alcohol dependent individuals and 46 socially drinking controls were exposed to three guided imageries: stress, alcohol cue and neutral. These were presented randomly across consecutive days. Plasma measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-10 (IL-10), were collected at baseline, immediately after imagery and at various recovery time-points. Ratings of alcohol craving, negative mood and anxiety were also obtained at the same time-points. Results The alcohol group demonstrated decreased basal IL-10 compared with controls particularly following exposure to alcohol cue. They also showed a dampened TNFα and TNFR1 response to stress and cue, respectively, and a generalized suppression of IL-6. In the alcohol group, these immune system adaptations occurred alongside significant elevations in anxiety, negative mood and alcohol craving. Conclusions Findings demonstrate that broad immuno-suppression is still observed in alcohol dependent individuals after three weeks of abstinence and may be linked to motivation for alcohol. PMID:28675117

  18. Forskolin suppresses delayed-rectifier K+ currents and enhances spike frequency-dependent adaptation of sympathetic neurons.

    Directory of Open Access Journals (Sweden)

    Luis I Angel-Chavez

    Full Text Available In signal transduction research natural or synthetic molecules are commonly used to target a great variety of signaling proteins. For instance, forskolin, a diterpene activator of adenylate cyclase, has been widely used in cellular preparations to increase the intracellular cAMP level. However, it has been shown that forskolin directly inhibits some cloned K+ channels, which in excitable cells set up the resting membrane potential, the shape of action potential and regulate repetitive firing. Despite the growing evidence indicating that K+ channels are blocked by forskolin, there are no studies yet assessing the impact of this mechanism of action on neuron excitability and firing patterns. In sympathetic neurons, we find that forskolin and its derivative 1,9-Dideoxyforskolin, reversibly suppress the delayed rectifier K+ current (IKV. Besides, forskolin reduced the spike afterhyperpolarization and enhanced the spike frequency-dependent adaptation. Given that IKV is mostly generated by Kv2.1 channels, HEK-293 cells were transfected with cDNA encoding for the Kv2.1 α subunit, to characterize the mechanism of forskolin action. Both drugs reversible suppressed the Kv2.1-mediated K+ currents. Forskolin inhibited Kv2.1 currents and IKV with an IC50 of ~32 μM and ~24 µM, respectively. Besides, the drug induced an apparent current inactivation and slowed-down current deactivation. We suggest that forskolin reduces the excitability of sympathetic neurons by enhancing the spike frequency-dependent adaptation, partially through a direct block of their native Kv2.1 channels.

  19. Dosage of boron traces in graphite, uranium and beryllium oxide; Dosage de traces de bore dans le graphite, l'uranium et l'oxyde de beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Coursier, J [Ecole Nationale Superieure de Physique et Chimie Industrielles, 75 - Paris (France); Hure, J; Platzer, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1955-07-01

    The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [French] Le probleme du dosage du bore dans les materiaux servant a la construction de reacteurs nucleaires se pose de la facon suivante: determiner a environ 0,1 ppm pres des quantites de bore de l'ordre de quelques dixiemes de ppm. Nous avons choisit la colorimetrie a la curcumine comme methode de dosage. Pour atteindre les teneurs indiquees, il est necessaire d'effectuer une separation prealable du bore et des materiaux de base, soit par extraction du fluoborate de tetraphenylarsonium dans le cas du dosage de bore dans l'uranium et l'oxyde de beryllium, soit par l'utilisation d'une resine echangeuse de cations dans le cas du graphite. (M.B.)

  20. Dosage compensation of serine-4 transfer RNA in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Birchler, J.A.; Owenby, R.K.; Jacobson, K.B.

    1982-01-01

    A dosage series of the X chromosome site for serine-4 transfer RNA consisting of one of three copies in females and one to two in males was constructed to test whether transfer RNA expression is governed by dosage compensation. A dosage effect on the level of the serine-4 isoacceptor was observed in both females and males when the structural locus was varied. However, in males, each dose had a relatively greater expression so the normal one dose was slightly greater than the total female value and the duplicated male had the highest relative expression of all the types examined. Serine-4 levels in males and females from an isogenic Oregon-R stock were similar. Thus the transfer RNA levels conform to the expectations of dosage compensation

  1. Evolution of vertebrate sex chromosomes and dosage compensation.

    Science.gov (United States)

    Graves, Jennifer A Marshall

    2016-01-01

    Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

  2. Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

    Science.gov (United States)

    Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

    2011-07-01

    In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

  3. Evaluation of insecticides in different dosages to control cicadas in parica plantations

    Directory of Open Access Journals (Sweden)

    Odineila Martins Monteiro

    2014-07-01

    Full Text Available This study aimed to determine the more efficient and economically viable dosage of chemical insecticide to control Quesada gigas (Hemiptera: Cicadidae nymphs in parica plantations. Three dosages of three products (carbofuran, imidacloprid and thiamethoxam were tested based on the maximum recommended dosage for the control of cicadas in coffee plants and applied in total area. The dosage of one kilogram of a commercial product based in thiamethoxam per hectare was more efficient economically and environmentally to control nymphs of Q. gigas in parica plantations.

  4. 21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

  5. New applications to computerized tomography: analysis of solid dosage forms produced by pharmaceutical industry

    International Nuclear Information System (INIS)

    Oliveira Junior, Jose Martins de; Martins, Antonio Cesar Germano

    2009-01-01

    Full text: In recent years, computerized tomography (CT) has been used as a new probe to study solid dosage forms (tablets) produced by pharmaceutical industry. This new approach to study tablet and powder, or granulation, properties used in pharmaceutical industry is very suitable. First because CT can generate information that traditional technologies used in this kind of analysis can not, such as, density distribution of internal structures and tablet dimensions, pore size distribution, particle shape information, and also investigation of official and unofficial (counterfeit) copies of solid dosage forms. Second because CT is a nondestructive technique, allowing the use of tablets or granules in others analysis. In this work we discus how CT can be used to acquire and reconstruct internal microstructure of tablets and granules. CT is a technique that is based on attenuation of X-rays passing through matter. Attenuation depends on the density and atomic number of the material that is scanned. In this work, a micro-CT X-ray scanner (manufactured by the group of Applied Nuclear Physics at University of Sorocaba) was used to obtain three-dimensional images of the tablets and granules for nondestructive analysis. These images showed a non uniform density distribution of material inside some tablets, the morphology of some granules analyzed, the integrity of the liquid-filled soft-gelatin capsule and so on. It could also be observed that the distribution of different constituents presents an osmotic controlled-release dosage form. The present work shows that it is possible to use X-ray microtomography to obtain useful qualitative and quantitative information on the structure of pharmaceutical dosage forms. (author)

  6. Alpha-1 Antitrypsin Prevents the Development of Preeclampsia Through Suppression of Oxidative Stress.

    Science.gov (United States)

    Feng, Yaling; Xu, Jianjuan; Zhou, Qin; Wang, Rong; Liu, Nin; Wu, Yanqun; Yuan, Hua; Che, Haisha

    2016-01-01

    Preeclampsia (PE) and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT) played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS, and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

  7. Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress

    Directory of Open Access Journals (Sweden)

    Yaling eFeng

    2016-05-01

    Full Text Available Preeclampsia (PE and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

  8. 21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

  9. New Spectrophotometric and Conductometric Methods for Macrolide Antibiotics Determination in Pure and Pharmaceutical Dosage Forms Using Rose Bengal

    Directory of Open Access Journals (Sweden)

    Rania A. Sayed

    2013-01-01

    Full Text Available Two Simple, accurate, precise, and rapid spectrophotometric and conductometric methods were developed for the estimation of erythromycin thiocyanate (I, clarithromycin (II, and azithromycin dihydrate (III in both pure and pharmaceutical dosage forms. The spectrophotometric procedure depends on the reaction of rose bengal and copper with the cited drugs to form stable ternary complexes which are extractable with methylene chloride, and the absorbances were measured at 558, 557, and 560 nm for (I, (II, and (III, respectively. The conductometric method depends on the formation of an ion-pair complex between the studied drug and rose bengal. For the spectrophotometric method, Beer's law was obeyed. The correlation coefficient ( for the studied drugs was found to be 0.9999. The molar absorptivity (, Sandell’s sensitivity, limit of detection (LOD, and limit of quantification (LOQ were also calculated. The proposed methods were successfully applied for the determination of certain pharmaceutical dosage forms containing the studied drugs

  10. Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation

    Science.gov (United States)

    Zhang, Yemin; Zhou, Yu; Li, Mingxin; Wang, Changhua

    2016-01-01

    Previous studies have evidenced that the anticancer potential of curcumin (diferuloylmethane), a main yellow bioactive compound from plant turmeric was mediated by interfering with PI3K/Akt signaling. However, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that curcumin treatment reduced Akt protein expression in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells, along with an activation of autophagy and suppression of ubiquitin-proteasome system (UPS) function. The curcumin-reduced Akt expression, cell proliferation, and migration were prevented by genetic and pharmacological inhibition of autophagy but not by UPS inhibition. Additionally, inactivation of AMPK by its specific inhibitor compound C or by target shRNA-mediated silencing attenuated curcumin-activated autophagy. Thus, these results indicate that curcumin-stimulated AMPK activity induces activation of the autophagy-lysosomal protein degradation pathway leading to Akt degradation and the subsequent suppression of proliferation and migration in breast cancer cell. PMID:26752181

  11. Automatic identification and normalization of dosage forms in drug monographs

    Science.gov (United States)

    2012-01-01

    Background Each day, millions of health consumers seek drug-related information on the Web. Despite some efforts in linking related resources, drug information is largely scattered in a wide variety of websites of different quality and credibility. Methods As a step toward providing users with integrated access to multiple trustworthy drug resources, we aim to develop a method capable of identifying drug's dosage form information in addition to drug name recognition. We developed rules and patterns for identifying dosage forms from different sections of full-text drug monographs, and subsequently normalized them to standardized RxNorm dosage forms. Results Our method represents a significant improvement compared with a baseline lookup approach, achieving overall macro-averaged Precision of 80%, Recall of 98%, and F-Measure of 85%. Conclusions We successfully developed an automatic approach for drug dosage form identification, which is critical for building links between different drug-related resources. PMID:22336431

  12. Onabotulinum toxin A dosage trends over time for adductor spasmodic dysphonia: A 15-year experience.

    Science.gov (United States)

    Tang, Christopher G; Novakovic, Daniel; Mor, Niv; Blitzer, Andrew

    2016-03-01

    Although onabotulinum neurotoxin A (BoNTA) has been used for over three decades for the treatment of adductor spasmodic dysphonia, no study has been performed to look at the trend of BoNTA dosages across time. The goal of this study is to evaluate the dosage trends to determine if the dosage necessary for voice improvement in patients increases over time. Charts were reviewed for patients with 15 years or more of experience. Linear regression analysis was performed to determine correlation coefficients and trends. Fifty-five patients receiving BoNTA injections by the senior author (a.b.) for over 15 years were evaluated. Thirty-nine patients (82% female) met inclusion criteria. Patients received injections over an average of 18.6 years ± 1.36 years, with the longest follow-up of 21.5 years. Of 39 patients, 16 (41%) had a negative correlation coefficient (Pearson's r) suggesting a decrease over time, whereas 23 (59%) had a positive correlation coefficient suggesting an increase over time. The mean correlation coefficient was 0.139 ± 0.534 and P  0.05 in 20 patients. R(2) for all patients were less than 0.75. Onabotulinum neurotoxin A injection dosage trends vary depending on the individual over time. Overall, the dose range appears to be stable in the majority of patients, suggesting that tolerance does not play a significant part in dose variation over time. 4. Laryngoscope, 126:678-681, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Evaluation of the effect of torsemide on warfarin dosage requirements.

    Science.gov (United States)

    Lai, Sophia; Momper, Jeremiah D; Yam, Felix K

    2017-08-01

    Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 ± 15 and 34 ± 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects.

  14. Serum-dependent expression of promyelocytic leukemia protein suppresses propagation of influenza virus

    International Nuclear Information System (INIS)

    Iki, Shigeo; Yokota, Shin-ichi; Okabayashi, Tamaki; Yokosawa, Noriko; Nagata, Kyosuke; Fujii, Nobuhiro

    2005-01-01

    The rate of propagation of influenza virus in human adenocarcinoma Caco-2 cells was found to negatively correlate with the concentration of fetal bovine serum (FBS) in the culture medium. Virus replicated more rapidly at lower FBS concentrations (0 or 2%) than at higher concentrations (10 or 20%) during an early stage of infection. Basal and interferon (IFN)-induced levels of typical IFN-inducible anti-viral proteins, such as 2',5'-oligoadenylate synthetase, dsRNA-activated protein kinase and MxA, were unaffected by variation in FBS concentrations. But promyelocytic leukemia protein (PML) was expressed in a serum-dependent manner. In particular, the 65 to 70 kDa isoform of PML was markedly upregulated following the addition of serum. In contrast, other isoforms were induced by IFN treatment, and weakly induced by FBS concentrations. Immunofluorescence microscopy indicated that PML was mainly formed nuclear bodies in Caco-2 cells at various FBS concentrations, and the levels of the PML-nuclear bodies were upregulated by FBS. Overexpression of PML isoform consisting of 560 or 633 amino acid residues by transfection of expression plasmid results in significantly delayed viral replication rate in Caco-2 cells. On the other hand, downregulation of PML expression by RNAi enhanced viral replication. These results indicate that PML isoforms which are expressed in a serum-dependent manner suppress the propagation of influenza virus at an early stage of infection

  15. Maximum Recommended Dosage of Lithium for Pregnant Women Based on a PBPK Model for Lithium Absorption

    Directory of Open Access Journals (Sweden)

    Scott Horton

    2012-01-01

    Full Text Available Treatment of bipolar disorder with lithium therapy during pregnancy is a medical challenge. Bipolar disorder is more prevalent in women and its onset is often concurrent with peak reproductive age. Treatment typically involves administration of the element lithium, which has been classified as a class D drug (legal to use during pregnancy, but may cause birth defects and is one of only thirty known teratogenic drugs. There is no clear recommendation in the literature on the maximum acceptable dosage regimen for pregnant, bipolar women. We recommend a maximum dosage regimen based on a physiologically based pharmacokinetic (PBPK model. The model simulates the concentration of lithium in the organs and tissues of a pregnant woman and her fetus. First, we modeled time-dependent lithium concentration profiles resulting from lithium therapy known to have caused birth defects. Next, we identified maximum and average fetal lithium concentrations during treatment. Then, we developed a lithium therapy regimen to maximize the concentration of lithium in the mother’s brain, while maintaining the fetal concentration low enough to reduce the risk of birth defects. This maximum dosage regimen suggested by the model was 400 mg lithium three times per day.

  16. Deconstructing continuous flash suppression.

    Science.gov (United States)

    Yang, Eunice; Blake, Randolph

    2012-03-08

    In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

  17. Effects of different dosages of propylene glycol in dry cows and cows in early lactation.

    Science.gov (United States)

    Maurer, Michaela; Peinhopf, Walter; Gottschalk, Jutta; Einspanier, Almut; Koeller, Gabor; Wittek, Thomas

    2017-11-01

    In this Research Paper we hypothesised that the temporary insulin resistance seen during the transition period in dairy cows may cause significant differences in the efficacy of PG at different sampling periods and that in some cases this effect will be dose dependent. Eighty four sampling sets were generated by studying 7 multiparous Holstein cows repeatedly at 4 sampling periods of 3 d length (dry cows: days 40, 39 and 38 antepartum; close up cows: days 10, 9 and 8 antepartum; fresh cows: days 3, 4 and 5 post-partum; lactating cows: days 38, 39 and 40 post-partum). On each of these days 3 h after morning feeding propylene glycol was drenched in different dosages of 100, 300 or 500 ml once per day (cross over study). The different doses were applied in an alternating order (Latin square). Blood samples were taken before, every 30 min up to 4 h, after 6 and 12 h after PG application. Following parameters have been measured: insulin, non-esterified fatty acids (NEFA), betahydroxybutyrate (BHB), bilirubin, cholesterol, potassium, aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Revised Quantitative Insulin Sensitivity Check Index (RQUICKI) was calculated. It was found that glucose, insulin, NEFA, BHB, bilirubin and potassium concentrations were influenced differently by the three defined dosages of propylene glycol at four different sampling periods. Whereas RQUICKI, cholesterol, AST and GLDH did not differ between the sampling periods and treatments. The major results of the study are that the effect of PG is dose-dependent and that the effect of PG is depending on the time of application according to calving. It can be concluded that in fresh cows higher dosages are necessary to provoke similar effects in comparison to dry, close up and lactating cows. Although the study did not compare to topdressing of PG from the results it is reasonable to believe that bolus application of a specific PG volume is necessary to provoke the effect.

  18. Modeled dosage-response relationship on the net photosynthetic rate for the sensitivity to acid rain of 21 plant species.

    Science.gov (United States)

    Deng, Shihuai; Gou, Shuzhen; Sun, Baiye; Lv, Wenlin; Li, Yuanwei; Peng, Hong; Xiao, Hong; Yang, Gang; Wang, Yingjun

    2012-08-01

    This study investigated the sensitivity of plant species to acid rain based on the modeled dosage-response relationship on the net photosynthetic rate (P (N)) of 21 types of plant species, subjected to the exposure of simulated acid rain (SAR) for 5 times during a period of 50 days. Variable responses of P (N) to SAR occurred depending on the type of plant. A majority (13 species) of the dosage-response relationship could be described by an S-shaped curve and be fitted with the Boltzmann model. Model fitting allowed quantitative evaluation of the dosage-response relationship and an accurate estimation of the EC(10), termed as the pH of the acid rain resulting in a P (N) 10 % lower than the reference value. The top 9 species (Camellia sasanqua, Cinnamomum camphora, etc. EC(10) ≤ 3.0) are highly endurable to very acid rain. The rare, relict plant Metasequoia glyptostroboides was the most sensitive species (EC(10) = 5.1) recommended for protection.

  19. Inelastic collisions and density-dependent excitation suppression in a 87Sr optical lattice clock

    International Nuclear Information System (INIS)

    Bishof, M.; Martin, M. J.; Swallows, M. D.; Benko, C.; Lin, Y.; Quemener, G.; Rey, A. M.; Ye, J.

    2011-01-01

    We observe two-body loss of 3 P 0 87 Sr atoms trapped in a one-dimensional optical lattice. We measure loss rate coefficients for atomic samples between 1 and 6 μK that are prepared either in a single nuclear-spin sublevel or with equal populations in two sublevels. The measured temperature and nuclear-spin preparation dependence of rate coefficients agree well with calculations and reveal that rate coefficients for distinguishable atoms are only slightly enhanced over those of indistinguishable atoms. We further observe a suppression of excitation and losses during interrogation of the 1 S 0 - 3 P 0 transition as density increases and Rabi frequency decreases, which suggests the presence of strong interactions in our dynamically driven many-body system.

  20. Tetrahydrobiopterin Has a Glucose-Lowering Effect by Suppressing Hepatic Gluconeogenesis in an Endothelial Nitric Oxide Synthase–Dependent Manner in Diabetic Mice

    Science.gov (United States)

    Abudukadier, Abulizi; Fujita, Yoshihito; Obara, Akio; Ohashi, Akiko; Fukushima, Toru; Sato, Yuichi; Ogura, Masahito; Nakamura, Yasuhiko; Fujimoto, Shimpei; Hosokawa, Masaya; Hasegawa, Hiroyuki; Inagaki, Nobuya

    2013-01-01

    Endothelial nitric oxide synthase (eNOS) dysfunction induces insulin resistance and glucose intolerance. Tetrahydrobiopterin (BH4) is an essential cofactor of eNOS that regulates eNOS activity. In the diabetic state, BH4 is oxidized to 7,8-dihydrobiopterin, which leads to eNOS dysfunction owing to eNOS uncoupling. The current study investigates the effects of BH4 on glucose metabolism and insulin sensitivity in diabetic mice. Single administration of BH4 lowered fasting blood glucose levels in wild-type mice with streptozotocin (STZ)-induced diabetes and alleviated eNOS dysfunction by increasing eNOS dimerization in the liver of these mice. Liver has a critical role in glucose-lowering effects of BH4 through suppression of hepatic gluconeogenesis. BH4 activated AMP kinase (AMPK), and the suppressing effect of BH4 on gluconeogenesis was AMPK-dependent. In addition, the glucose-lowering effect and activation of AMPK by BH4 did not appear in mice with STZ-induced diabetes lacking eNOS. Consecutive administration of BH4 in ob/ob mice ameliorated glucose intolerance and insulin resistance. Taken together, BH4 suppresses hepatic gluconeogenesis in an eNOS-dependent manner, and BH4 has a glucose-lowering effect as well as an insulin-sensitizing effect in diabetic mice. BH4 has potential in the treatment of type 2 diabetes. PMID:23649519

  1. Locoregional injection of F-18 radiopharmaceuticals suppresses tumor xenograft growth in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wong, C -L [The Univ. of Texas M.D. Anderson Cancer Center, Texas (United States)

    2004-07-01

    The energetic positrons (0.633 Mev) from F-18 dissipate kinetic energies before annihilation to produce two 0.511 Mev photons which also contribute to the radiation absorbed dose to the surroundings. In living organism, the contribution from the positron itself to the surrounding tissues (up to 2 mm) is larger than from the 2 photons. Apoptosis has been reported in rat tumors after systemic injection of F-18 FDG although no growth retardation was noted. This study is designed to exploit the pharmacokinetic advantages of locoregional injection of positron emitters in the suppression of tumor growth in rats. Methods: Groups of Fisher 344 adult female rats were inoculated with rat mammary tumors (100,000 cells) intramuscularly (IM) in the thigh. Locoregional injection with F-18 NaF or F-18 FDG was accomplished in days 3 or 7 with single doses of increasing strengths (0.2 to 3 mCi). Tumor growth rates were noted and compared to control (sham injection with saline). The locoregional distribution and clearance of F-18 were estimated from serial tomograms using a Concord MicroPET (R4) after intramuscular injection of 0.1-0.2 mCi of F-18 NaF or F-18 FDG in groups of triplicate rats. Results: A dose-related pattern of tumor suppression is noted with F-18 FDG, whether treatment occurs in day 3 or 7 after inoculation. Additional experiment of injection of 5 mci of F-18 FDG at day 14 also suppressed the growth of a well-formed tumor. Tumor suppression by F-18 NaF is less obvious and only occurs with high dose (2 mCi). MicroPET images demonstrate that F-18 FDG is retained in the injection site while F-18 NaF dissipates rapidly. Conclusion: Locoregional injection of positron-emitters may be sufficient to suppress tumor growth. The mechanism is likely related to the pharmacokinetic profile of the compound within the tissue. Discussion: Locoregional application of radionuclides may provide feasible alternatives to slow tumor growth or prevent tumor recurrence. The use of

  2. Application of DBNPA dosage for biofouling control in spiral wound membrane systems

    KAUST Repository

    Siddiqui, Amber

    2017-05-30

    Biocides may be used to control biofouling in spiral-wound reverse osmosis (RO) and nanofiltration (NF) systems. The objective of this study was to investigate the effect of biocide 2,2-dibromo-3-ni-trilopropionamide (DBNPA) dosage on biofouling control. Preventive biofouling control was studied applying a continuous dosage of substrate (0.5 mg/L) and DBNPA (1 mg/L). Curative biofouling control was studied on pre-grown biofilms, once again applying a continuous dosage of substrate (0.5 mg acetate C/L) and DBNPA (1 and 20 mg/L). Biofouling studies were performed in membrane fouling simulators (MFSs) supplied with biodegradable substrate and DBNPA. The pressure drop was monitored in time and at the end of the study, the accumulated biomass in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can be managed by preventive DBNPA dosage. For biofouled systems, continuous dosage of DBNPA (1 and 20 mg/L) inactivated the accumulated biomass but did not restore the original pressure drop and did not remove the accumulated inactive cells and extracellular polymeric substances (EPS), indicating DBNPA dosage is not suitable for curative biofouling control.

  3. Quality of 'Climax' blueberries after low dosage electron beam irradiation

    International Nuclear Information System (INIS)

    Miller, W.R.; McDonald, R.E.; McCollum, T.G.; Smittle, B.J.

    1994-01-01

    Fruit of 'Climax' rabbiteye blueberries (Vaccinium ashei Reade) were irradiated by a linear accelerator at 0, 0.25, 0.5, 0.75, 1.0, and 1.25 kGy and evaluated for various quality attributes after storage for 1, 3, 7, or 14 days at 1C plus 2 days at 15C, respectively. Weight loss increased during storage and averaged 4.2% after the final inspection and was not affected by irradiation dosage. About 5% of total berries were decayed after 14 days at 1C, about 6% after the final inspection at 15C, but decay was not affected by the level of irradiation. Electrolyte leakage, skin color, total soluble solids, acidity, and pH were also not affected by irradiation dosage. There was a significant decline in berry firmness, flavor, and texture as dosage increased. Berries treated at 1.0 kGy or above were softer and had lower flavor and texture preference scores than berries treated at lower dosages or nontreated berries

  4. Suppression of hypoxia inducible factor-1α (HIF-1α) by YC-1 is dependent on murine double minute 2 (Mdm2)

    International Nuclear Information System (INIS)

    Lau, C.K.; Yang, Z.F.; Lam, C.T.; Tam, K.H.; Poon, R.T.P.; Fan, S.T.

    2006-01-01

    Inhibition of HIF-1α activity provides an important strategy for the treatment of cancer. Recently, 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) has been identified as an anti-HIF-1α drug in cancer therapy with unclear molecular mechanism. In the present study, we aimed to investigate the effect and mechanism of YC-1 on HIF-1α in a hepatocellular carcinoma cell line under hypoxic condition, which was generated by incubating cells with 0.1% O 2 . The phenotypic and molecular changes of cells were determined by cell proliferation assay, apoptosis assay, luciferase promoter assay, and Western blot analysis. YC-1 arrested tumor cell growth in a dose-dependent manner, whereas it did not induce cell apoptosis. Hypoxia-induced upregulation of HIF-1α was suppressed by YC-1 administration. YC-1 inhibited HIF-1α protein synthesis under normoxia and affected protein stability under hypoxia. YC-1 suppressed the expression of total and phosphorylated forms of murine double minute 2 (Mdm2), whereas this inhibitory effect was blocked by overexpression of Mdm2. In conclusion, YC-1 suppressed both protein synthesis and stability of HIF-1α in HCC cells, and its inhibitory effects on HIF-1α were dependent on Mdm2

  5. Fenofibrate suppressed proliferation and migration of human neuroblastoma cells via oxidative stress dependent of TXNIP upregulation

    Energy Technology Data Exchange (ETDEWEB)

    Su, Cunjin; Shi, Aiming; Cao, Guowen [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Tao, Tao [Department of Urology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009 (China); Chen, Ruidong [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Hu, Zhanhong; Shen, Zhu; Tao, Hong; Cao, Bin [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Hu, Duanmin, E-mail: hudmsdfey@sina.com [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Bao, Junjie, E-mail: baojjsdfey@sina.com [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China)

    2015-05-15

    There are no appropriate drugs for metastatic neuroblastoma (NB), which is the most common extra-cranial solid tumor for childhood. Thioredoxin binding protein (TXNIP), the endogenous inhibitor of ROS elimination, has been identified as a tumor suppressor in various solid tumors. It reported that fenofibrate exerts anti-tumor effects in several human cancer cell lines. However, its detail mechanisms remain unclear. The present study assessed the effects of fenofibrate on NB cells and investigated TXNIP role in its anti-tumor mechanisms. We used MTT assay to detect cells proliferation, starch wound test to investigate cells migration, H{sub 2}DCF-DA to detect intracellular ROS, siRNA to interfere TXNIP and peroxisome proliferator-androgen receptor-alpha (PPAR-α) expression, western blot to determine protein levels, flow cytometry to analyze apoptosis. Fenofibrate suppressed proliferation and migration of NB cells, remarkably increased intracellular ROS, upregulated TXNIP expression, promoted cell apoptosis. Furthermore, inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. Our results indicated the anti-tumor role of fenofibrate on NB cells by exacerbating oxidative stress and inducing apoptosis was dependent on the upregulation of TXNIP. - Highlights: • We found that fenofibrate suppressed proliferation and migration of NB cells. • We found that fenofibrate remarkably increased intracellular ROS, upregulated TXNIP expression, and promoted cell apoptosis. • Inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. • Our results indicated the anti-tumor role of fenofibrate on NB cells was dependent on the upregulation of TXNIP.

  6. Protocatechuic aldehyde attenuates cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation

    Directory of Open Access Journals (Sweden)

    Li Gao

    2016-12-01

    Full Text Available Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress and programmed cell death of renal tubular epithelial cells. All of which lead to higher mortality rates in patients. In this study we examined the protective effect of protocatechuic aldehyde (PA in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza. Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA largely blocked cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients with cisplatin treatment.

  7. Training-dependent cognitive advantage is suppressed at high altitude.

    Science.gov (United States)

    Li, Peng; Zhang, Gang; You, Hai-Yan; Zheng, Ran; Gao, Yu-Qi

    2012-06-25

    Ascent to high altitude is associated with decreases in cognitive function and work performance as a result of hypoxia. Some workers with special jobs typically undergo intensive mental training because they are expected to be agile, stable and error-free in their job performance. The purpose of this study was to determine the risk to cognitive function acquired from training following hypoxic exposure. The results of WHO neurobehavioral core tests battery (WHO-NCTB) and Raven's standard progressive matrices (RSPM) tests of a group of 54 highly trained military operators were compared with those of 51 non-trained ordinary people and were investigated at sea level and on the fifth day after arrival at high altitudes (3900m). Meanwhile, the plasma levels of brain-derived neurotrophic factor (BDNF), interleukin 1β (IL-1β) and vascular endothelial growth factor (VEGF) were examined. The result showed that at sea level, the trained group exhibited significantly better performance on neurobehavioral and RSPM tests. At high altitude, both groups had decreased accuracy in most cognitive tests and took longer to finish them. More importantly, the highly trained subjects showed more substantial declines than the non-trained subjects in visual reaction accuracy, auditory reaction speed, digit symbol scores, ability to report correct dots in a pursuit aiming test and total RSPM scores. This means that the training-dependent cognitive advantages in these areas were suppressed at high altitudes. The above phenomenon maybe associated with decreased BDNF and elevated inflammatory factor during hypoxia, and other mechanisms could not be excluded. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Dosage compensation and demasculinization of X chromosomes in Drosophila.

    Science.gov (United States)

    Bachtrog, Doris; Toda, Nicholas R T; Lockton, Steven

    2010-08-24

    The X chromosome of Drosophila shows a deficiency of genes with male-biased expression, whereas mammalian X chromosomes are enriched for spermatogenesis genes expressed premeiosis and multicopy testis genes. Meiotic X-inactivation and sexual antagonism can only partly account for these patterns. Here, we show that dosage compensation (DC) in Drosophila may contribute substantially to the depletion of male genes on the X. To equalize expression between X-linked and autosomal genes in the two sexes, male Drosophila hypertranscribe their single X, whereas female mammals silence one of their two X chromosomes. We combine fine-scale mapping data of dosage compensated regions with genome-wide expression profiles and show that most male-biased genes on the D. melanogaster X are located outside dosage compensated regions. Additionally, X-linked genes that have newly acquired male-biased expression in D. melanogaster are less likely to be dosage compensated, and parental X-linked genes that gave rise to an autosomal male-biased retrocopy are more likely located within compensated regions. This suggests that DC contributes to the observed demasculinization of X chromosomes in Drosophila, both by limiting the emergence of male-biased expression patterns of existing X genes, and by contributing to gene trafficking of male genes off the X. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Vitamin K3 suppressed inflammatory and immune responses in a redox-dependent manner.

    Science.gov (United States)

    Checker, Rahul; Sharma, Deepak; Sandur, Santosh K; Khan, Nazir M; Patwardhan, Raghavendra S; Kohli, Vineet; Sainis, Krishna B

    2011-08-01

    Recent investigations suggest that cellular redox status may play a key role in the regulation of several immune functions. Treatment of lymphocytes with vitamin K3 (menadione) resulted in a significant decrease in cellular GSH/GSSG ratio and concomitant increase in the ROS levels. It also suppressed Concanavalin A (Con A)-induced proliferation and cytokine production in lymphocytes and CD4 + T cells in vitro. Immunosuppressive effects of menadione were abrogated only by thiol containing antioxidants. Mass spectrometric analysis showed that menadione directly interacted with thiol antioxidant GSH. Menadione completely suppressed Con A-induced activation of ERK, JNK and NF-κB in lymphocytes. It also significantly decreased the homeostasis driven proliferation of syngeneic CD4 + T cells. Further, menadione significantly delayed graft-vs-host disease morbidity and mortality in mice. Menadione suppressed phytohemagglutinin-induced cytokine production in human peripheral blood mononuclear cells. These results reveal that cellular redox perturbation by menadione is responsible for significant suppression of lymphocyte responses.

  10. The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

    Science.gov (United States)

    Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

    2013-10-02

    Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver

  11. Dosage of boron traces in graphite, uranium and beryllium oxide

    International Nuclear Information System (INIS)

    Coursier, J.; Hure, J.; Platzer, R.

    1955-01-01

    The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [fr

  12. TaS2 nanosheet-based room-temperature dosage meter for nitric oxide

    Directory of Open Access Journals (Sweden)

    Qiyuan He

    2014-09-01

    Full Text Available A miniature dosage meter for toxic gas is developed based on TaS2 nanosheets, which is capable of indicating the toxic dosage of trace level NO at room temperature. The TaS2 film-based chemiresistor shows an irreversible current response against the exposure of NO. The unique non-recovery characteristic makes the TaS2 film-based device an ideal indicator of total dosage of chronicle exposure.

  13. A brief history of dosage compensation

    Indian Academy of Sciences (India)

    depression of X-linked gene activity in the female, as well as by hyperexpression of the ... to the Harvey lecture, Muller had presented important ideas relative to dosage ... at Columbia. I do recall a talk by the popular physical anthro- pologist ...

  14. Activity of Simulated Human Dosage Regimens of Meropenem and Vaborbactam against Carbapenem-Resistant Enterobacteriaceae in an In Vitro Hollow-Fiber Model.

    Science.gov (United States)

    Sabet, Mojgan; Tarazi, Ziad; Rubio-Aparicio, Debora; Nolan, Thomas G; Parkinson, Jonathan; Lomovskaya, Olga; Dudley, Michael N; Griffith, David C

    2018-02-01

    The objective of these studies was to evaluate the exposures of meropenem and vaborbactam that would produce antibacterial activity and prevent resistance development in carbapenem-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains when tested at an inoculum of 10 8 CFU/ml. Thirteen K. pneumoniae isolates, three Enterobacter cloacae isolates, and one Escherichia coli isolate were examined in an in vitro hollow-fiber model over 32 h. Simulated dosage regimens of 1 to 2 g of meropenem with 1 to 2 g of vaborbactam, with meropenem administered every 8 h by a 3-h infusion based on phase 1 or phase 3 patient pharmacokinetic data, were studied in the model. A dosage of 2 g of meropenem in combination with 2 g of vaborbactam was bactericidal against K. pneumoniae , E. cloacae , and E. coli strains, with meropenem-vaborbactam MICs of up to 8 mg/liter. When the vaborbactam exposure was adjusted to the levels observed in patients enrolled in phase 3 trials (24-h free AUC, ∼550 mg · h/liter, versus 320 mg · h/liter in the phase 1 studies), 2 g of meropenem with 2 g of vaborbactam was also bactericidal against strains with meropenem-vaborbactam MICs of 16 mg/liter. In addition, this level of vaborbactam also suppressed the development of resistance observed using phase 1 exposures. In this pharmacodynamic model, exposures similar to 2 g of meropenem in combination with 2 g of vaborbactam administered every 8 h by a 3-h infusion in phase 3 trials produced antibacterial activity and suppressed the development of resistance against carbapenem-resistant KPC-producing strains of Enterobacteriaceae . Copyright © 2018 American Society for Microbiology.

  15. Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

    Science.gov (United States)

    Flemenbaum, A

    1976-05-01

    The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

  16. Influence of the fuel and dosage on the performance of double-compartment microbial fuel cells.

    Science.gov (United States)

    Asensio, Y; Fernandez-Marchante, C M; Lobato, J; Cañizares, P; Rodrigo, M A

    2016-08-01

    This manuscript focuses on the evaluation of the use of different types and dosages of fuels in the performance of double-compartment microbial fuel cell equipped with carbon felt electrodes and cationic membrane. Five types of fuels (ethanol, glycerol, acetate, propionate and fructose) have been tested for the same organic load (5,000 mg L(-1) measured as COD) and for one of them (acetate), the range of dosages between 500 and 20,000 mg L(-1) of COD was also studied. Results demonstrate that production of electricity depends strongly on the fuel used. Carboxylic acids are much more efficient than alcohols or fructose for the same organic load and within the range 500-5,000 mg L(-1) of acetate the production of electricity increases linearly with the amount of acetate fed but over these concentrations a change in the population composition may explain a worse performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. p53-Dependent suppression of genome instability in germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Otozai, Shinji [Department of Otorhinolaryngology and Head and Neck Surgery, Osaka University School of Medicine, Osaka 565-0871 (Japan); Ishikawa-Fujiwara, Tomoko [Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, B4, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Oda, Shoji [Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562 (Japan); Kamei, Yasuhiro [Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, B4, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ryo, Haruko [Nomura Project, National Institute of Biomedical Innovation, Osaka 565-0085 (Japan); Sato, Ayuko [Department of Pathology, Hyogo College of Medicine, Hyogo 663-8501 (Japan); Nomura, Taisei [Nomura Project, National Institute of Biomedical Innovation, Osaka 565-0085 (Japan); Mitani, Hiroshi [Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562 (Japan); Tsujimura, Tohru [Department of Pathology, Hyogo College of Medicine, Hyogo 663-8501 (Japan); Inohara, Hidenori [Department of Otorhinolaryngology and Head and Neck Surgery, Osaka University School of Medicine, Osaka 565-0871 (Japan); Todo, Takeshi, E-mail: todo@radbio.med.osaka-u.ac.jp [Department of Radiation Biology and Medical Genetics, Graduate School of Medicine, Osaka University, B4, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2014-02-15

    Highlights: • Radiation-induced microsatellite instability (MSI) was investigated in medaka fish. • msh2{sup −/−} fish had a high frequency of spontaneous MSI. • p53{sup −/−} fish had a high frequency of radiation-induced MSI. • p53 and msh2 suppress MSI by different pathways: mismatch removal and apoptosis. - Abstract: Radiation increases mutation frequencies at tandem repeat loci. Germline mutations in γ-ray-irradiated medaka fish (Oryzias latipes) were studied, focusing on the microsatellite loci. Mismatch-repair genes suppress microsatellite mutation by directly removing altered sequences at the nucleotide level, whereas the p53 gene suppresses genetic alterations by eliminating damaged cells. The contribution of these two defense mechanisms to radiation-induced microsatellite instability was addressed. The spontaneous mutation frequency was significantly higher in msh2{sup −/−} males than in wild-type fish, whereas there was no difference in the frequency of radiation-induced mutations between msh2{sup −/−} and wild-type fish. By contrast, irradiated p53{sup −/−} fish exhibited markedly increased mutation frequencies, whereas their spontaneous mutation frequency was the same as that of wild-type fish. In the spermatogonia of the testis, radiation induced a high level of apoptosis both in wild-type and msh2{sup −/−} fish, but negligible levels in p53{sup −/−} fish. The results demonstrate that the msh2 and p53 genes protect genome integrity against spontaneous and radiation-induced mutation by two different pathways: direct removal of mismatches and elimination of damaged cells.

  18. p53-Dependent suppression of genome instability in germ cells

    International Nuclear Information System (INIS)

    Otozai, Shinji; Ishikawa-Fujiwara, Tomoko; Oda, Shoji; Kamei, Yasuhiro; Ryo, Haruko; Sato, Ayuko; Nomura, Taisei; Mitani, Hiroshi; Tsujimura, Tohru; Inohara, Hidenori; Todo, Takeshi

    2014-01-01

    Highlights: • Radiation-induced microsatellite instability (MSI) was investigated in medaka fish. • msh2 −/− fish had a high frequency of spontaneous MSI. • p53 −/− fish had a high frequency of radiation-induced MSI. • p53 and msh2 suppress MSI by different pathways: mismatch removal and apoptosis. - Abstract: Radiation increases mutation frequencies at tandem repeat loci. Germline mutations in γ-ray-irradiated medaka fish (Oryzias latipes) were studied, focusing on the microsatellite loci. Mismatch-repair genes suppress microsatellite mutation by directly removing altered sequences at the nucleotide level, whereas the p53 gene suppresses genetic alterations by eliminating damaged cells. The contribution of these two defense mechanisms to radiation-induced microsatellite instability was addressed. The spontaneous mutation frequency was significantly higher in msh2 −/− males than in wild-type fish, whereas there was no difference in the frequency of radiation-induced mutations between msh2 −/− and wild-type fish. By contrast, irradiated p53 −/− fish exhibited markedly increased mutation frequencies, whereas their spontaneous mutation frequency was the same as that of wild-type fish. In the spermatogonia of the testis, radiation induced a high level of apoptosis both in wild-type and msh2 −/− fish, but negligible levels in p53 −/− fish. The results demonstrate that the msh2 and p53 genes protect genome integrity against spontaneous and radiation-induced mutation by two different pathways: direct removal of mismatches and elimination of damaged cells

  19. Implication of p53-dependent cellular senescence related gene, TARSH in tumor suppression

    International Nuclear Information System (INIS)

    Wakoh, Takeshi; Uekawa, Natsuko; Terauchi, Kunihiko; Sugimoto, Masataka; Ishigami, Akihito; Shimada, Jun-ichi; Maruyama, Mitsuo

    2009-01-01

    A novel target of NESH-SH3 (TARSH) was identified as a cellular senescence related gene in mouse embryonic fibroblasts (MEFs) replicative senescence, the expression of which has been suppressed in primary clinical lung cancer specimens. However, the molecular mechanism underlying the regulation of TARSH involved in pulmonary tumorigenesis remains unclear. Here we demonstrate that the reduction of TARSH gene expression by short hairpin RNA (shRNA) system robustly inhibited the MEFs proliferation with increase in senescence-associated β-galactosidase (SA-β-gal) activity. Using p53 -/- MEFs, we further suggest that this growth arrest by loss of TARSH is evoked by p53-dependent p21 Cip1 accumulation. Moreover, we also reveal that TARSH reduction induces multicentrosome in MEFs, which is linked in chromosome instability and tumor development. These results suggest that TARSH plays an important role in proliferation of replicative senescence and may serve as a trigger of tumor development.

  20. 21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

  1. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Aralia elata (Miquel) Seemann Suppresses Inflammatory ...

    African Journals Online (AJOL)

    ISSN: 1596-5996 (print); 1596-9827 (electronic) ... The LPS-induced increase in the production of nitric oxide was concentration- dependently suppressed ... Aralia elata ethanol extract (AEE) exhibits protective ... temperature for 72 h and filtered. The filtered .... scavenging activity in a dose-dependent manner showing a ...

  3. Centrality dependence of high-$p_{\\rm T}$ D meson suppression in Pb-Pb collisions at $\\sqrt{s_{\\rm NN}}$ = 2.76 TeV

    CERN Document Server

    Adam, Jaroslav; Aggarwal, Madan Mohan; Aglieri Rinella, Gianluca; Agnello, Michelangelo; Agrawal, Neelima; Ahammed, Zubayer; Ahn, Sang Un; Aimo, Ilaria; Aiola, Salvatore; Ajaz, Muhammad; Akindinov, Alexander; Alam, Sk Noor; Aleksandrov, Dmitry; Alessandro, Bruno; Alexandre, Didier; Alfaro Molina, Jose Ruben; Alici, Andrea; Alkin, Anton; Millan Almaraz, Jesus Roberto; Alme, Johan; Alt, Torsten; Altinpinar, Sedat; Altsybeev, Igor; Alves Garcia Prado, Caio; Andrei, Cristian; Andronic, Anton; Anguelov, Venelin; Anielski, Jonas; Anticic, Tome; Antinori, Federico; Antonioli, Pietro; Aphecetche, Laurent Bernard; Appelshaeuser, Harald; Arcelli, Silvia; Armesto Perez, Nestor; Arnaldi, Roberta; Arsene, Ionut Cristian; Arslandok, Mesut; Audurier, Benjamin; Augustinus, Andre; Averbeck, Ralf Peter; Azmi, Mohd Danish; Bach, Matthias Jakob; Badala, Angela; Baek, Yong Wook; Bagnasco, Stefano; Bailhache, Raphaelle Marie; Bala, Renu; Baldisseri, Alberto; Baltasar Dos Santos Pedrosa, Fernando; Baral, Rama Chandra; Barbano, Anastasia Maria; Barbera, Roberto; Barile, Francesco; Barnafoldi, Gergely Gabor; Barnby, Lee Stuart; Ramillien Barret, Valerie; Bartalini, Paolo; Barth, Klaus; Bartke, Jerzy Gustaw; Bartsch, Esther; Basile, Maurizio; Bastid, Nicole; Basu, Sumit; Bathen, Bastian; Batigne, Guillaume; Batista Camejo, Arianna; Batyunya, Boris; Batzing, Paul Christoph; Bearden, Ian Gardner; Beck, Hans; Bedda, Cristina; Behera, Nirbhay Kumar; Belikov, Iouri; Bellini, Francesca; Bello Martinez, Hector; Bellwied, Rene; Belmont Iii, Ronald John; Belmont Moreno, Ernesto; Belyaev, Vladimir; Bencedi, Gyula; Beole, Stefania; Berceanu, Ionela; Bercuci, Alexandru; Berdnikov, Yaroslav; Berenyi, Daniel; Bertens, Redmer Alexander; Berzano, Dario; Betev, Latchezar; Bhasin, Anju; Bhat, Inayat Rasool; Bhati, Ashok Kumar; Bhattacharjee, Buddhadeb; Bhom, Jihyun; Bianchi, Livio; Bianchi, Nicola; Bianchin, Chiara; Bielcik, Jaroslav; Bielcikova, Jana; Bilandzic, Ante; Biswas, Rathijit; Biswas, Saikat; Bjelogrlic, Sandro; Blanco, Fernando; Blau, Dmitry; Blume, Christoph; Bock, Friederike; Bogdanov, Alexey; Boggild, Hans; Boldizsar, Laszlo; Bombara, Marek; Book, Julian Heinz; Borel, Herve; Borissov, Alexander; Borri, Marcello; Bossu, Francesco; Botta, Elena; Boettger, Stefan; Braun-Munzinger, Peter; Bregant, Marco; Breitner, Timo Gunther; Broker, Theo Alexander; Browning, Tyler Allen; Broz, Michal; Brucken, Erik Jens; Bruna, Elena; Bruno, Giuseppe Eugenio; Budnikov, Dmitry; Buesching, Henner; Bufalino, Stefania; Buncic, Predrag; Busch, Oliver; Buthelezi, Edith Zinhle; Bashir Butt, Jamila; Buxton, Jesse Thomas; Caffarri, Davide; Cai, Xu; Caines, Helen Louise; Calero Diaz, Liliet; Caliva, Alberto; Calvo Villar, Ernesto; Camerini, Paolo; Carena, Francesco; Carena, Wisla; Castillo Castellanos, Javier Ernesto; Castro, Andrew John; Casula, Ester Anna Rita; Cavicchioli, Costanza; Ceballos Sanchez, Cesar; Cepila, Jan; Cerello, Piergiorgio; Cerkala, Jakub; Chang, Beomsu; Chapeland, Sylvain; Chartier, Marielle; Charvet, Jean-Luc Fernand; Chattopadhyay, Subhasis; Chattopadhyay, Sukalyan; Chelnokov, Volodymyr; Cherney, Michael Gerard; Cheshkov, Cvetan Valeriev; Cheynis, Brigitte; Chibante Barroso, Vasco Miguel; Dobrigkeit Chinellato, David; Chochula, Peter; Choi, Kyungeon; Chojnacki, Marek; Choudhury, Subikash; Christakoglou, Panagiotis; Christensen, Christian Holm; Christiansen, Peter; Chujo, Tatsuya; Chung, Suh-Urk; Zhang, Chunhui; Cicalo, Corrado; Cifarelli, Luisa; Cindolo, Federico; Cleymans, Jean Willy Andre; Colamaria, Fabio Filippo; Colella, Domenico; Collu, Alberto; Colocci, Manuel; Conesa Balbastre, Gustavo; Conesa Del Valle, Zaida; Connors, Megan Elizabeth; Contreras Nuno, Jesus Guillermo; Cormier, Thomas Michael; Corrales Morales, Yasser; Cortes Maldonado, Ismael; Cortese, Pietro; Cosentino, Mauro Rogerio; Costa, Filippo; Crochet, Philippe; Cruz Albino, Rigoberto; Cuautle Flores, Eleazar; Cunqueiro Mendez, Leticia; Dahms, Torsten; Dainese, Andrea; Danu, Andrea; Das, Debasish; Das, Indranil; Das, Supriya; Dash, Ajay Kumar; Dash, Sadhana; De, Sudipan; De Caro, Annalisa; De Cataldo, Giacinto; De Cuveland, Jan; De Falco, Alessandro; De Gruttola, Daniele; De Marco, Nora; De Pasquale, Salvatore; Deisting, Alexander; Deloff, Andrzej; Denes, Ervin Sandor; D'Erasmo, Ginevra; Di Bari, Domenico; Di Mauro, Antonio; Di Nezza, Pasquale; Diaz Corchero, Miguel Angel; Dietel, Thomas; Dillenseger, Pascal; Divia, Roberto; Djuvsland, Oeystein; Dobrin, Alexandru Florin; Dobrowolski, Tadeusz Antoni; Domenicis Gimenez, Diogenes; Donigus, Benjamin; Dordic, Olja; Dubey, Anand Kumar; Dubla, Andrea; Ducroux, Laurent; Dupieux, Pascal; Ehlers Iii, Raymond James; Elia, Domenico; Engel, Heiko; Erazmus, Barbara Ewa; Erdemir, Irem; Erhardt, Filip; Eschweiler, Dominic; Espagnon, Bruno; Estienne, Magali Danielle; Esumi, Shinichi; Eum, Jongsik; Evans, David; Evdokimov, Sergey; Eyyubova, Gyulnara; Fabbietti, Laura; Fabris, Daniela; Faivre, Julien; Fantoni, Alessandra; Fasel, Markus; Feldkamp, Linus; Felea, Daniel; Feliciello, Alessandro; Feofilov, Grigorii; Ferencei, Jozef; Fernandez Tellez, Arturo; Gonzalez Ferreiro, Elena; Ferretti, Alessandro; Festanti, Andrea; Feuillard, Victor Jose Gaston; Figiel, Jan; Araujo Silva Figueredo, Marcel; Filchagin, Sergey; Finogeev, Dmitry; Fiore, Enrichetta Maria; Fleck, Martin Gabriel; Floris, Michele; Foertsch, Siegfried Valentin; Foka, Panagiota; Fokin, Sergey; Fragiacomo, Enrico; Francescon, Andrea; Frankenfeld, Ulrich Michael; Fuchs, Ulrich; Furget, Christophe; Furs, Artur; Fusco Girard, Mario; Gaardhoeje, Jens Joergen; Gagliardi, Martino; Gago Medina, Alberto Martin; Gallio, Mauro; Gangadharan, Dhevan Raja; Ganoti, Paraskevi; Gao, Chaosong; Garabatos Cuadrado, Jose; Garcia-Solis, Edmundo Javier; Gargiulo, Corrado; Gasik, Piotr Jan; Germain, Marie; Gheata, Andrei George; Gheata, Mihaela; Ghosh, Premomoy; Ghosh, Sanjay Kumar; Gianotti, Paola; Giubellino, Paolo; Giubilato, Piero; Gladysz-Dziadus, Ewa; Glassel, Peter; Gomez Ramirez, Andres; Gonzalez Zamora, Pedro; Gorbunov, Sergey; Gorlich, Lidia Maria; Gotovac, Sven; Grabski, Varlen; Graczykowski, Lukasz Kamil; Graham, Katie Leanne; Grelli, Alessandro; Grigoras, Alina Gabriela; Grigoras, Costin; Grigoryev, Vladislav; Grigoryan, Ara; Grigoryan, Smbat; Grynyov, Borys; Grion, Nevio; Grosse-Oetringhaus, Jan Fiete; Grossiord, Jean-Yves; Grosso, Raffaele; Guber, Fedor; Guernane, Rachid; Guerzoni, Barbara; Gulbrandsen, Kristjan Herlache; Gulkanyan, Hrant; Gunji, Taku; Gupta, Anik; Gupta, Ramni; Haake, Rudiger; Haaland, Oystein Senneset; Hadjidakis, Cynthia Marie; Haiduc, Maria; Hamagaki, Hideki; Hamar, Gergoe; Hansen, Alexander; Harris, John William; Hartmann, Helvi; Harton, Austin Vincent; Hatzifotiadou, Despina; Hayashi, Shinichi; Heckel, Stefan Thomas; Heide, Markus Ansgar; Helstrup, Haavard; Herghelegiu, Andrei Ionut; Herrera Corral, Gerardo Antonio; Hess, Benjamin Andreas; Hetland, Kristin Fanebust; Hilden, Timo Eero; Hillemanns, Hartmut; Hippolyte, Boris; Hosokawa, Ritsuya; Hristov, Peter Zahariev; Huang, Meidana; Humanic, Thomas; Hussain, Nur; Hussain, Tahir; Hutter, Dirk; Hwang, Dae Sung; Ilkaev, Radiy; Ilkiv, Iryna; Inaba, Motoi; Ippolitov, Mikhail; Irfan, Muhammad; Ivanov, Marian; Ivanov, Vladimir; Izucheev, Vladimir; Jacobs, Peter Martin; Jadlovska, Slavka; Jahnke, Cristiane; Jang, Haeng Jin; Janik, Malgorzata Anna; Pahula Hewage, Sandun; Jena, Chitrasen; Jena, Satyajit; Jimenez Bustamante, Raul Tonatiuh; Jones, Peter Graham; Jung, Hyungtaik; Jusko, Anton; Kalinak, Peter; Kalweit, Alexander Philipp; Kamin, Jason Adrian; Kang, Ju Hwan; Kaplin, Vladimir; Kar, Somnath; Karasu Uysal, Ayben; Karavichev, Oleg; Karavicheva, Tatiana; Karayan, Lilit; Karpechev, Evgeny; Kebschull, Udo Wolfgang; Keidel, Ralf; Keijdener, Darius Laurens; Keil, Markus; Khan, Kamal; Khan, Mohammed Mohisin; Khan, Palash; Khan, Shuaib Ahmad; Khanzadeev, Alexei; Kharlov, Yury; Kileng, Bjarte; Kim, Beomkyu; Kim, Do Won; Kim, Dong Jo; Kim, Hyeonjoong; Kim, Jinsook; Kim, Mimae; Kim, Minwoo; Kim, Se Yong; Kim, Taesoo; Kirsch, Stefan; Kisel, Ivan; Kiselev, Sergey; Kisiel, Adam Ryszard; Kiss, Gabor; Klay, Jennifer Lynn; Klein, Carsten; Klein, Jochen; Klein-Boesing, Christian; Kluge, Alexander; Knichel, Michael Linus; Knospe, Anders Garritt; Kobayashi, Taiyo; Kobdaj, Chinorat; Kofarago, Monika; Kollegger, Thorsten; Kolozhvari, Anatoly; Kondratev, Valerii; Kondratyeva, Natalia; Kondratyuk, Evgeny; Konevskikh, Artem; Kopcik, Michal; Kour, Mandeep; Kouzinopoulos, Charalampos; Kovalenko, Oleksandr; Kovalenko, Vladimir; Kowalski, Marek; Koyithatta Meethaleveedu, Greeshma; Kral, Jiri; Kralik, Ivan; Kravcakova, Adela; Krelina, Michal; Kretz, Matthias; Krivda, Marian; Krizek, Filip; Kryshen, Evgeny; Krzewicki, Mikolaj; Kubera, Andrew Michael; Kucera, Vit; Kugathasan, Thanushan; Kuhn, Christian Claude; Kuijer, Paulus Gerardus; Kulakov, Igor; Kumar, Ajay; Kumar, Jitendra; Lokesh, Kumar; Kurashvili, Podist; Kurepin, Alexander; Kurepin, Alexey; Kuryakin, Alexey; Kushpil, Svetlana; Kweon, Min Jung; Kwon, Youngil; La Pointe, Sarah Louise; La Rocca, Paola; Lagana Fernandes, Caio; Lakomov, Igor; Langoy, Rune; Lara Martinez, Camilo Ernesto; Lardeux, Antoine Xavier; Lattuca, Alessandra; Laudi, Elisa; Lea, Ramona; Leardini, Lucia; Lee, Graham Richard; Lee, Seongjoo; Legrand, Iosif; Lehas, Fatiha; Lemmon, Roy Crawford; Lenti, Vito; Leogrande, Emilia; Leon Monzon, Ildefonso; Leoncino, Marco; Levai, Peter; Li, Shuang; Li, Xiaomei; Lien, Jorgen Andre; Lietava, Roman; Lindal, Svein; Lindenstruth, Volker; Lippmann, Christian; Lisa, Michael Annan; Ljunggren, Hans Martin; Lodato, Davide Francesco; Lonne, Per-Ivar; Loginov, Vitaly; Loizides, Constantinos; Lopez, Xavier Bernard; Lopez Torres, Ernesto; Lowe, Andrew John; Luettig, Philipp Johannes; Lunardon, Marcello; Luparello, Grazia; Ferreira Natal Da Luz, Pedro Hugo; Maevskaya, Alla; Mager, Magnus; Mahajan, Sanjay; Mahmood, Sohail Musa; Maire, Antonin; Majka, Richard Daniel; Malaev, Mikhail; Maldonado Cervantes, Ivonne Alicia; Malinina, Liudmila; Mal'Kevich, Dmitry; Malzacher, Peter; Mamonov, Alexander; Manko, Vladislav; Manso, Franck; Manzari, Vito; Marchisone, Massimiliano; Mares, Jiri; Margagliotti, Giacomo Vito; Margotti, Anselmo; Margutti, Jacopo; Marin, Ana Maria; Markert, Christina; Marquard, Marco; Martin, Nicole Alice; Martin Blanco, Javier; Martinengo, Paolo; Martinez Hernandez, Mario Ivan; Martinez-Garcia, Gines; Martinez Pedreira, Miguel; Martynov, Yevgen; Mas, Alexis Jean-Michel; Masciocchi, Silvia; Masera, Massimo; Masoni, Alberto; Massacrier, Laure Marie; Mastroserio, Annalisa; Masui, Hiroshi; Matyja, Adam Tomasz; Mayer, Christoph; Mazer, Joel Anthony; Mazzoni, Alessandra Maria; Mcdonald, Daniel; Meddi, Franco; Melikyan, Yuri; Menchaca-Rocha, Arturo Alejandro; Meninno, Elisa; Mercado-Perez, Jorge; Meres, Michal; Miake, Yasuo; Mieskolainen, Matti Mikael; Mikhaylov, Konstantin; Milano, Leonardo; Milosevic, Jovan; Minervini, Lazzaro Manlio; Mischke, Andre; Mishra, Aditya Nath; Miskowiec, Dariusz Czeslaw; Mitra, Jubin; Mitu, Ciprian Mihai; Mohammadi, Naghmeh; Mohanty, Bedangadas; Molnar, Levente; Montano Zetina, Luis Manuel; Montes Prado, Esther; Morando, Maurizio; Moreira De Godoy, Denise Aparecida; Moretto, Sandra; Morreale, Astrid; Morsch, Andreas; Muccifora, Valeria; Mudnic, Eugen; Muhlheim, Daniel Michael; Muhuri, Sanjib; Mukherjee, Maitreyee; Mulligan, James Declan; Gameiro Munhoz, Marcelo; Murray, Sean; Musa, Luciano; Musinsky, Jan; Nandi, Basanta Kumar; Nania, Rosario; Nappi, Eugenio; Naru, Muhammad Umair; Nattrass, Christine; Nayak, Kishora; Nayak, Tapan Kumar; Nazarenko, Sergey; Nedosekin, Alexander; Nellen, Lukas; Ng, Fabian; Nicassio, Maria; Niculescu, Mihai; Niedziela, Jeremi; Nielsen, Borge Svane; Nikolaev, Sergey; Nikulin, Sergey; Nikulin, Vladimir; Noferini, Francesco; Nomokonov, Petr; Nooren, Gerardus; Cabanillas Noris, Juan Carlos; Norman, Jaime; Nyanin, Alexander; Nystrand, Joakim Ingemar; Oeschler, Helmut Oskar; Oh, Saehanseul; Oh, Sun Kun; Ohlson, Alice Elisabeth; Okatan, Ali; Okubo, Tsubasa; Olah, Laszlo; Oleniacz, Janusz; Oliveira Da Silva, Antonio Carlos; Oliver, Michael Henry; Onderwaater, Jacobus; Oppedisano, Chiara; Orava, Risto; Ortiz Velasquez, Antonio; Oskarsson, Anders Nils Erik; Otwinowski, Jacek Tomasz; Oyama, Ken; Ozdemir, Mahmut; Pachmayer, Yvonne Chiara; Pagano, Paola; Paic, Guy; Pajares Vales, Carlos; Pal, Susanta Kumar; Pan, Jinjin; Pandey, Ashutosh Kumar; Pant, Divyash; Papcun, Peter; Papikyan, Vardanush; Pappalardo, Giuseppe; Pareek, Pooja; Park, Woojin; Parmar, Sonia; Passfeld, Annika; Paticchio, Vincenzo; Patra, Rajendra Nath; Paul, Biswarup; Peitzmann, Thomas; Pereira Da Costa, Hugo Denis Antonio; Pereira De Oliveira Filho, Elienos; Peresunko, Dmitry Yurevich; Perez Lara, Carlos Eugenio; Perez Lezama, Edgar; Peskov, Vladimir; Pestov, Yury; Petracek, Vojtech; Petrov, Viacheslav; Petrovici, Mihai; Petta, Catia; Piano, Stefano; Pikna, Miroslav; Pillot, Philippe; Pinazza, Ombretta; Pinsky, Lawrence; Piyarathna, Danthasinghe; Ploskon, Mateusz Andrzej; Planinic, Mirko; Pluta, Jan Marian; Pochybova, Sona; Podesta Lerma, Pedro Luis Manuel; Poghosyan, Martin; Polishchuk, Boris; Poljak, Nikola; Poonsawat, Wanchaloem; Pop, Amalia; Porteboeuf, Sarah Julie; Porter, R Jefferson; Pospisil, Jan; Prasad, Sidharth Kumar; Preghenella, Roberto; Prino, Francesco; Pruneau, Claude Andre; Pshenichnov, Igor; Puccio, Maximiliano; Puddu, Giovanna; Pujahari, Prabhat Ranjan; Punin, Valery; Putschke, Jorn Henning; Qvigstad, Henrik; Rachevski, Alexandre; Raha, Sibaji; Rajput, Sonia; Rak, Jan; Rakotozafindrabe, Andry Malala; Ramello, Luciano; Raniwala, Rashmi; Raniwala, Sudhir; Rasanen, Sami Sakari; Rascanu, Bogdan Theodor; Rathee, Deepika; Read, Kenneth Francis; Real, Jean-Sebastien; Redlich, Krzysztof; Reed, Rosi Jan; Rehman, Attiq Ur; Reichelt, Patrick Simon; Reidt, Felix; Ren, Xiaowen; Renfordt, Rainer Arno Ernst; Reolon, Anna Rita; Reshetin, Andrey; Rettig, Felix Vincenz; Revol, Jean-Pierre; Reygers, Klaus Johannes; Riabov, Viktor; Ricci, Renato Angelo; Richert, Tuva Ora Herenui; Richter, Matthias Rudolph; Riedler, Petra; Riegler, Werner; Riggi, Francesco; Ristea, Catalin-Lucian; Rivetti, Angelo; Rocco, Elena; Rodriguez Cahuantzi, Mario; Rodriguez Manso, Alis; Roeed, Ketil; Rogochaya, Elena; Rohr, David Michael; Roehrich, Dieter; Romita, Rosa; Ronchetti, Federico; Ronflette, Lucile; Rosnet, Philippe; Rossi, Andrea; Roukoutakis, Filimon; Roy, Ankhi; Roy, Christelle Sophie; Roy, Pradip Kumar; Rubio Montero, Antonio Juan; Rui, Rinaldo; Russo, Riccardo; Ryabinkin, Evgeny; Ryabov, Yury; Rybicki, Andrzej; Sadovskiy, Sergey; Safarik, Karel; Sahlmuller, Baldo; Sahoo, Pragati; Sahoo, Raghunath; Sahoo, Sarita; Sahu, Pradip Kumar; Saini, Jogender; Sakai, Shingo; Saleh, Mohammad Ahmad; Salgado Lopez, Carlos Alberto; Salzwedel, Jai Samuel Nielsen; Sambyal, Sanjeev Singh; Samsonov, Vladimir; Sanchez Castro, Xitzel; Sandor, Ladislav; Sandoval, Andres; Sano, Masato; Sarkar, Debojit; Scapparone, Eugenio; Scarlassara, Fernando; Scharenberg, Rolf Paul; Schiaua, Claudiu Cornel; Schicker, Rainer Martin; Schmidt, Christian Joachim; Schmidt, Hans Rudolf; Schuchmann, Simone; Schukraft, Jurgen; Schulc, Martin; Schuster, Tim Robin; Schutz, Yves Roland; Schwarz, Kilian Eberhard; Schweda, Kai Oliver; Scioli, Gilda; Scomparin, Enrico; Scott, Rebecca Michelle; Seeder, Karin Soraya; Seger, Janet Elizabeth; Sekiguchi, Yuko; Sekihata, Daiki; Selyuzhenkov, Ilya; Senosi, Kgotlaesele; Seo, Jeewon; Serradilla Rodriguez, Eulogio; Sevcenco, Adrian; Shabanov, Arseniy; Shabetai, Alexandre; Shadura, Oksana; Shahoyan, Ruben; Shangaraev, Artem; Sharma, Ankita; Sharma, Mona; Sharma, Monika; Sharma, Natasha; Shigaki, Kenta; Shtejer Diaz, Katherin; Sibiryak, Yury; Siddhanta, Sabyasachi; Sielewicz, Krzysztof Marek; Siemiarczuk, Teodor; Silvermyr, David Olle Rickard; Silvestre, Catherine Micaela; Simatovic, Goran; Simonetti, Giuseppe; Singaraju, Rama Narayana; Singh, Ranbir; Singha, Subhash; Singhal, Vikas; Sinha, Bikash; Sarkar - Sinha, Tinku; Sitar, Branislav; Sitta, Mario; Skaali, Bernhard; Slupecki, Maciej; Smirnov, Nikolai; Snellings, Raimond; Snellman, Tomas Wilhelm; Soegaard, Carsten; Soltz, Ron Ariel; Song, Jihye; Song, Myunggeun; Song, Zixuan; Soramel, Francesca; Sorensen, Soren Pontoppidan; Spacek, Michal; Spiriti, Eleuterio; Sputowska, Iwona Anna; Spyropoulou-Stassinaki, Martha; Srivastava, Brijesh Kumar; Stachel, Johanna; Stan, Ionel; Stefanek, Grzegorz; Steinpreis, Matthew Donald; Stenlund, Evert Anders; Steyn, Gideon Francois; Stiller, Johannes Hendrik; Stocco, Diego; Strmen, Peter; Alarcon Do Passo Suaide, Alexandre; Sugitate, Toru; Suire, Christophe Pierre; Suleymanov, Mais Kazim Oglu; Sultanov, Rishat; Sumbera, Michal; Symons, Timothy; Szabo, Alexander; Szanto De Toledo, Alejandro; Szarka, Imrich; Szczepankiewicz, Adam; Szymanski, Maciej Pawel; Takahashi, Jun; Tanaka, Naoto; Tangaro, Marco-Antonio; Tapia Takaki, Daniel Jesus; Tarantola Peloni, Attilio; Tarhini, Mohamad; Tariq, Mohammad; Tarzila, Madalina-Gabriela; Tauro, Arturo; Tejeda Munoz, Guillermo; Telesca, Adriana; Terasaki, Kohei; Terrevoli, Cristina; Teyssier, Boris; Thaeder, Jochen Mathias; Thomas, Deepa; Tieulent, Raphael Noel; Timmins, Anthony Robert; Toia, Alberica; Trogolo, Stefano; Trubnikov, Victor; Trzaska, Wladyslaw Henryk; Tsuji, Tomoya; Tumkin, Alexandr; Turrisi, Rosario; Tveter, Trine Spedstad; Ullaland, Kjetil; Uras, Antonio; Usai, Gianluca; Utrobicic, Antonija; Vajzer, Michal; Vala, Martin; Valencia Palomo, Lizardo; Vallero, Sara; Van Der Maarel, Jasper; Van Hoorne, Jacobus Willem; Van Leeuwen, Marco; Vanat, Tomas; Vande Vyvre, Pierre; Varga, Dezso; Diozcora Vargas Trevino, Aurora; Vargyas, Marton; Varma, Raghava; Vasileiou, Maria; Vasiliev, Andrey; Vauthier, Astrid; Vechernin, Vladimir; Veen, Annelies Marianne; Veldhoen, Misha; Velure, Arild; Venaruzzo, Massimo; Vercellin, Ermanno; Vergara Limon, Sergio; Vernet, Renaud; Verweij, Marta; Vickovic, Linda; Viesti, Giuseppe; Viinikainen, Jussi Samuli; Vilakazi, Zabulon; Villalobos Baillie, Orlando; Vinogradov, Alexander; Vinogradov, Leonid; Vinogradov, Yury; Virgili, Tiziano; Vislavicius, Vytautas; Viyogi, Yogendra; Vodopyanov, Alexander; Volkl, Martin Andreas; Voloshin, Kirill; Voloshin, Sergey; Volpe, Giacomo; Von Haller, Barthelemy; Vorobyev, Ivan; Vranic, Danilo; Vrlakova, Janka; Vulpescu, Bogdan; Vyushin, Alexey; Wagner, Boris; Wagner, Jan; Wang, Hongkai; Wang, Mengliang; Wang, Yifei; Watanabe, Daisuke; Watanabe, Yosuke; Weber, Michael; Weber, Steffen Georg; Wessels, Johannes Peter; Westerhoff, Uwe; Wiechula, Jens; Wikne, Jon; Wilde, Martin Rudolf; Wilk, Grzegorz Andrzej; Wilkinson, Jeremy John; Williams, Crispin; Windelband, Bernd Stefan; Winn, Michael Andreas; Yaldo, Chris G; Yang, Hongyan; Yang, Ping; Yano, Satoshi; Yin, Zhongbao; Yokoyama, Hiroki; Yoo, In-Kwon; Yurchenko, Volodymyr; Yushmanov, Igor; Zaborowska, Anna; Zaccolo, Valentina; Zaman, Ali; Zampolli, Chiara; Correia Zanoli, Henrique Jose; Zaporozhets, Sergey; Zardoshti, Nima; Zarochentsev, Andrey; Zavada, Petr; Zavyalov, Nikolay; Zbroszczyk, Hanna Paulina; Zgura, Sorin Ion; Zhalov, Mikhail; Zhang, Haitao; Zhang, Xiaoming; Zhang, Yonghong; Zhao, Chengxin; Zhigareva, Natalia; Zhou, Daicui; Zhou, You; Zhou, Zhuo; Zhu, Hongsheng; Zhu, Jianhui; Zhu, Xiangrong; Zichichi, Antonino; Zimmermann, Alice; Zimmermann, Markus Bernhard; Zinovjev, Gennady; Zyzak, Maksym

    2015-11-30

    The nuclear modification factor, $R_{\\rm AA}$, of the prompt charmed mesons ${\\rm D^0}$, ${\\rm D^+}$ and ${\\rm D^{*+}}$, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at a centre-of-mass energy $\\sqrt{s_{\\rm NN}} = 2.76$ TeV in two transverse momentum intervals, $5suppression of a factor of 5-6 in the 10% most central collisions. The suppression and its centrality dependence are compatible within uncertainties with those of charged pions. A comparison with the $R_{\\rm AA}$ of non-prompt ${\\rm J}/\\psi$ from B meson decays, measured by the CMS Collaboration, hints at a larger suppression of D mesons in the most central collisions.

  4. Thyroxin hormone suppression treatment

    International Nuclear Information System (INIS)

    Samuel, A.M.

    1999-01-01

    One of the important modalities of treatment of thyroid cancer (TC) after surgery is the administration of thyroxin as an adjuvant treatment. The analysis supports the theory that thyroid suppression plays an important role in patient management. 300 μg of thyroxin, as this is an adequate dose for suppression is given. Ideally the dose should be tailored by testing s-TSH levels. However, since a large number of the patients come from out station cities and villages this is impractical. We therefore depend on clinical criteria of hyperthyroid symptoms and adjust the dose. Very few patients need such adjustment

  5. Tyr phosphatase-mediated P-ERK inhibition suppresses senescence in EIA + v-raf transformed cells, which, paradoxically, are apoptosis-protected in a MEK-dependent manner.

    Science.gov (United States)

    De Vitis, Stefania; Sonia Treglia, Antonella; Ulianich, Luca; Turco, Stefano; Terrazzano, Giuseppe; Lombardi, Angela; Miele, Claudia; Garbi, Corrado; Beguinot, Francesco; Di Jeso, Bruno

    2011-02-01

    Activation of the Ras-Raf-extracellular signal-regulated kinase (ERK) pathway causes not only proliferation and suppression of apoptosis but also the antioncogenic response of senescence. How these contrasting effects are reconciled to achieve cell transformation and cancer formation is poorly understood. In a system of two-step carcinogenesis (dedifferentiated PC EIA, transformed PC EIA-polyoma-middle T [PC EIA + Py] and PC EIA-v-raf [PC EIA + raf] cells], v-raf cooperated with EIA by virtue of a strong prosurvival effect, not elicited by Py-middle T, evident toward serum-deprivation-and H(2)O(2)-induced apoptosis. Apoptosis was detected by DNA fragmentation and annexin V staining. The prosurvival function of v-raf was, in part, mitogen-activated protein kinase/ERK kinase (MEK)-dependent, as shown by pharmacological MEK inhibition. The MEK-dependent antiapoptotic effect of v-raf was exerted despite a lower level of P-ERK1/2 in EIA + raf cells with respect to EIA + Py/EIA cells, which was dependent on a high tyrosine phosphatase activity, as shown by orthovanadate blockade. An ERK1/2 tyrosine phosphatase was likely involved. The high tyrosine phosphatase activity was instrumental to the complete suppression of senescence, detected by β-galactosidase activity, because tyrosine phosphatase blockade induced senescence in EIA + raf but not in EIA + Py cells. High tyrosine phosphatase activity and evasion from senescence were confirmed in an anaplastic thyroid cancer cell line. Therefore, besides EIA, EIA + raf cells suppress senescence through a new mechanism, namely, phosphatase-mediated P-ERK1/2 inhibition, but, paradoxically, retain the oncogenic effects of the Raf-ERK pathway. We propose that the survival effect of Raf is not a function of absolute P-ERK1/2 levels at a given time but is rather dynamically dependent on greater variations after an apoptotic stimulus.

  6. Tyr Phosphatase-Mediated P-ERK Inhibition Suppresses Senescence in EIA + v-raf Transformed Cells, Which, Paradoxically, Are Apoptosis-Protected in a MEK-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Stefania De Vitis

    2011-02-01

    Full Text Available Activation of the Ras-Raf-extracellular signal-regulated kinase (ERK pathway causes not only proliferation and suppression of apoptosis but also the antioncogenic response of senescence. How these contrasting effects are reconciled to achieve cell transformation and cancer formation is poorly understood. In a system of two-step carcinogenesis (dedifferentiated PC EIA, transformed PC EIA-polyoma-middle T [PC EIA + Py] and PC EIA-v-raf [PC EIA + raf] cells], v-raf cooperated with EIA by virtue of a strong prosurvival effect, not elicited by Py-middle T, evident toward serum-deprivation-and H2O2-induced apoptosis. Apoptosis was detected by DNA fragmentation and annexin V staining. The prosurvival function of v-raf was, in part, mitogen-activated protein kinase/ERK kinase (MEK-dependent, as shown by pharmacological MEK inhibition. The MEK-dependent antiapoptotic effect of v-raf was exerted despite a lower level of P-ERK1/2 in EIA + raf cells with respect to EIA + Py/EIA cells, which was dependent on a high tyrosine phosphatase activity, as shown by orthovanadate blockade. An ERK1/2 tyrosine phosphatase was likely involved. The high tyrosine phosphatase activity was instrumental to the complete suppression of senescence, detected by β-galactosidase activity, because tyrosine phosphatase blockade induced senescence in EIA + raf but not in EIA + Py cells. High tyrosine phosphatase activity and evasion from senescence were confirmed in an anaplastic thyroid cancer cell line. Therefore, besides EIA, EIA + raf cells suppress senescence through a new mechanism, namely, phosphatase-mediated P-ERK1/2 inhibition, but, paradoxically, retain the oncogenic effects of the Raf-ERK pathway. We propose that the survival effect of Raf is not a function of absolute P-ERK1/2 levels at a given time but is rather dynamically dependent on greater variations after an apoptotic stimulus.

  7. Cross-cultural differences in emotion suppression in everyday interactions.

    Science.gov (United States)

    Huwaë, Sylvia; Schaafsma, Juliette

    2016-05-11

    Previous research suggests that in collectivistic cultures, people tend to suppress their emotions more than in individualistic cultures. Little research, however, has explored cross-cultural differences in emotion regulation in everyday interactions. Using a daily social interaction method, we examined whether people from collectivistic backgrounds (Chinese exchange students and immigrants from the Moluccas, Indonesia) living in the Netherlands differed from those from individualistic backgrounds (Dutch natives) in emotion suppression during everyday interactions. We also examined whether this depended on their relationship with the interaction partner(s). We found that Chinese participants suppressed positive and negative emotions more than Dutch and Moluccan participants and that this was related to differences in interdependent and independent self-construal across the samples. We also found that Chinese participants suppressed positive emotions less in interactions with close others, whereas Dutch participants suppressed negative emotions more with non-close others. No such differences were found for Moluccans. Our findings support the idea that people from collectivistic cultures suppress emotions more than those from individualistic cultures, but they also suggest that this depends on who the interaction partner is. Furthermore, they suggest that emotion suppression may change when people with collectivistic backgrounds have been raised in individualistic cultures. © 2016 International Union of Psychological Science.

  8. Short-time, high-dosage penicillin infusion therapy of syphilis

    DEFF Research Database (Denmark)

    Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming

    2003-01-01

    The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

  9. GENE-dosage effects on fitness in recent adaptive duplications: ace-1 in the mosquito Culex pipiens.

    Science.gov (United States)

    Labbé, Pierrick; Milesi, Pascal; Yébakima, André; Pasteur, Nicole; Weill, Mylène; Lenormand, Thomas

    2014-07-01

    Gene duplications have long been advocated to contribute to the evolution of new functions. The role of selection in their early spread is more controversial. Unless duplications are favored for a direct benefit of increased expression, they are likely detrimental. In this article, we investigated the case of duplications favored because they combine already functionally divergent alleles. Their gene-dosage/fitness relations are poorly known because selection may operate on both overall expression and duplicates relative dosage. Using the well-documented case of Culex pipiens resistance to insecticides, we compared strains with various ace-1 allele combinations, including two duplicated alleles carrying both susceptible and resistant copies. The overall protein activity was nearly additive, but, surprisingly, fitness correlated better with the relative proportion of susceptible and resistant copies rather than any absolute measure of activity. Gene dosage is thus crucial, duplications stabilizing a "heterozygote" phenotype. It corroborates the view that these were favored because they fix a permanent heterosis, thereby solving the irreducible trade-off between resistance and synaptic transmission. Moreover, we showed that the contrasted successes of the two duplicated alleles in natural populations depend on genetic changes unrelated to ace-1, confirming the probable implication of recessive sublethal mutations linked to structural rearrangements in some duplications. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  10. Genetic basis for dosage sensitivity in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Isabelle M Henry

    2007-04-01

    Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

  11. Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback

    Directory of Open Access Journals (Sweden)

    Larson Charles R

    2011-06-01

    Full Text Available Abstract Background The motor-driven predictions about expected sensory feedback (efference copies have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs were recorded in response to upward pitch shift stimuli (PSS with five different magnitudes (0, +50, +100, +200 and +400 cents at voice onset during active vocal production and passive listening to the playback. Results Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents, became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Conclusions Findings of the present study suggest that the brain utilizes the motor predictions (efference copies to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds.

  12. Error-dependent modulation of speech-induced auditory suppression for pitch-shifted voice feedback.

    Science.gov (United States)

    Behroozmand, Roozbeh; Larson, Charles R

    2011-06-06

    The motor-driven predictions about expected sensory feedback (efference copies) have been proposed to play an important role in recognition of sensory consequences of self-produced motor actions. In the auditory system, this effect was suggested to result in suppression of sensory neural responses to self-produced voices that are predicted by the efference copies during vocal production in comparison with passive listening to the playback of the identical self-vocalizations. In the present study, event-related potentials (ERPs) were recorded in response to upward pitch shift stimuli (PSS) with five different magnitudes (0, +50, +100, +200 and +400 cents) at voice onset during active vocal production and passive listening to the playback. Results indicated that the suppression of the N1 component during vocal production was largest for unaltered voice feedback (PSS: 0 cents), became smaller as the magnitude of PSS increased to 200 cents, and was almost completely eliminated in response to 400 cents stimuli. Findings of the present study suggest that the brain utilizes the motor predictions (efference copies) to determine the source of incoming stimuli and maximally suppresses the auditory responses to unaltered feedback of self-vocalizations. The reduction of suppression for 50, 100 and 200 cents and its elimination for 400 cents pitch-shifted voice auditory feedback support the idea that motor-driven suppression of voice feedback leads to distinctly different sensory neural processing of self vs. non-self vocalizations. This characteristic may enable the audio-vocal system to more effectively detect and correct for unexpected errors in the feedback of self-produced voice pitch compared with externally-generated sounds.

  13. Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

    Directory of Open Access Journals (Sweden)

    Thanos Manos

    2018-04-01

    Full Text Available In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce

  14. Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

    Science.gov (United States)

    Manos, Thanos; Zeitler, Magteld; Tass, Peter A

    2018-01-01

    In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long

  15. A step toward development of printable dosage forms for poorly soluble drugs

    DEFF Research Database (Denmark)

    Raijada, Dharaben Kaushikkumar; Genina, Natalja; Fors, Daniela

    2013-01-01

    The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...

  16. Maths anxiety and medication dosage calculation errors: A scoping review.

    Science.gov (United States)

    Williams, Brett; Davis, Samantha

    2016-09-01

    A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is important for healthcare students to overcome this barrier when calculating drug dosages in order to avoid administering the incorrect dose to a patient when in the clinical setting. The aim of this study was to examine the effects of maths anxiety on healthcare students' ability to accurately calculate drug dosages by performing a scoping review of the existing literature. This review utilised a six-stage methodology using the following databases; CINAHL, Embase, Medline, Scopus, PsycINFO, Google Scholar, Trip database (http://www.tripdatabase.com/) and Grey Literature report (http://www.greylit.org/). After an initial title/abstract review of relevant papers, and then full text review of the remaining papers, six articles were selected for inclusion in this study. Of the six articles included, there were three experimental studies, two quantitative studies and one mixed method study. All studies addressed nursing students and the presence of maths anxiety. No relevant studies from other disciplines were identified in the existing literature. Three studies took place in the U.S, the remainder in Canada, Australia and United Kingdom. Upon analysis of these studies, four factors including maths anxiety were identified as having an influence on a student's drug dosage calculation abilities. Ultimately, the results from this review suggest more research is required in nursing and other relevant healthcare disciplines regarding the effects of maths anxiety on drug dosage calculations. This additional knowledge will be important to further inform development of strategies to decrease the potentially serious effects of errors in drug dosage calculation to patient safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms

    Directory of Open Access Journals (Sweden)

    Evert Fuenmayor

    2018-04-01

    Full Text Available Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

  18. Gleditsia Saponin C Induces A549 Cell Apoptosis via Caspase-Dependent Cascade and Suppresses Tumor Growth on Xenografts Tumor Animal Model

    Directory of Open Access Journals (Sweden)

    Ye Cheng

    2018-01-01

    Full Text Available Saponins are natural compounds and possess the most promising anti-cancer function. Here, a saponin gleditsia saponin C (GSC, extracted from gleditsiae fructus abnormalis, could induce apoptosis of lung tumor cell line A549 via caspase dependent cascade and this effect could be prevented by the caspase inhibitors. In addition, GSC induced cell death companied with an increase ratio of Bax:Bcl-2 and inhibition of ERK and Akt signaling pathways. Meanwhile, GSC suppressed TNFα inducing NF-κB activation and increased the susceptibility of lung cancer cell to TNFα induced apoptosis. Furthermore, on mouse xenograft model, GSC significantly suppressed tumor growth and induced cancer cell apoptosis, which validated the anti-tumor effect of GSC. Based on these results, GSC might be a promising drug candidate of anti-lung cancer for its potential clinical applications.

  19. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Liang Y

    2016-05-01

    Full Text Available Yayun Liang,1 Benford Mafuvadze,1 Johannes D Aebi,2 Salman M Hyder1 1Dalton Cardiovascular Research Center and Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, MO, USA; 2Medicinal Chemistry, Roche Pharma Research and Early Development (pRED, Roche Innovation Center Basel, F Hoffmann-La Roche Ltd., Basel, Switzerland Abstract: Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration; however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4'-[6-(allylmethylaminohexyloxy]-4-bromo-2'-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071 (RO, which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway, on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the

  20. Low-dosage helical CT applications for chest medical checkup and lung cancer screening

    International Nuclear Information System (INIS)

    Wang Ping; Cui Fa; Liang Huanqing; Zheng Minfei

    2005-01-01

    Objective: A discussion on low-dosage helical CT applications on chest medical checkup and lung cancer screening. Methods: On the 100 chest medical check up with three different of protocols, including standard-dosage (the tube current was 230 mAs) were compared with low-dose (tube current was 50 mAs or 30 mAs). Results: Low-dosage helical CT scan provides excellent images. In 100 chest medical checkup, 39 nodules or masses were revealed, enlarged lymph node was noted in 1 case; emphysema or bullae was demonstrated in 3 segments; thickening of bronchial wall was shown in 2 cases; and localized pleural thickening was found in 1 case. Conclusion: In chest checkup or lung cancer screening low-dosage helical CT (tube current 30 mAs) will not only guarantee image quality but also reduce the radiation dose during the examination. (authors)

  1. QR encoded smart oral dosage forms by inkjet printing.

    Science.gov (United States)

    Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

    2018-01-30

    The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. B cells exposed to enterobacterial components suppress development of experimental colitis

    DEFF Research Database (Denmark)

    Schmidt, Esben Gjerløff Wedebye; Larsen, Hjalte List; Kristensen, Nanna Ny

    2012-01-01

    ). RESULTS: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed...... development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-¿)-producing T(H) 1 cells and increased frequencies of Foxp3......-expressing T cells. CONCLUSIONS: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way. (Inflamm Bowel Dis 2011;)....

  3. Suppressed visual looming stimuli are not integrated with auditory looming signals: Evidence from continuous flash suppression.

    Science.gov (United States)

    Moors, Pieter; Huygelier, Hanne; Wagemans, Johan; de-Wit, Lee; van Ee, Raymond

    2015-01-01

    Previous studies using binocular rivalry have shown that signals in a modality other than the visual can bias dominance durations depending on their congruency with the rivaling stimuli. More recently, studies using continuous flash suppression (CFS) have reported that multisensory integration influences how long visual stimuli remain suppressed. In this study, using CFS, we examined whether the contrast thresholds for detecting visual looming stimuli are influenced by a congruent auditory stimulus. In Experiment 1, we show that a looming visual stimulus can result in lower detection thresholds compared to a static concentric grating, but that auditory tone pips congruent with the looming stimulus did not lower suppression thresholds any further. In Experiments 2, 3, and 4, we again observed no advantage for congruent multisensory stimuli. These results add to our understanding of the conditions under which multisensory integration is possible, and suggest that certain forms of multisensory integration are not evident when the visual stimulus is suppressed from awareness using CFS.

  4. Dosage-based parameters for characterization of puff dispersion results.

    Science.gov (United States)

    Berbekar, Eva; Harms, Frank; Leitl, Bernd

    2015-01-01

    A set of parameters is introduced to characterize the dispersion of puff releases based on the measured dosage. These parameters are the dosage, peak concentration, arrival time, peak time, leaving time, ascent time, descent time and duration. Dimensionless numbers for the scaling of the parameters are derived from dimensional analysis. The dimensionless numbers are tested and confirmed based on a statistically representative wind tunnel dataset. The measurements were carried out in a 1:300 scale model of the Central Business District in Oklahoma City. Additionally, the effect of the release duration on the puff parameters is investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Spectrophotometric Determination of Trimipramine in Tablet Dosage ...

    African Journals Online (AJOL)

    Purpose: To develop and validate simple, rapid and sensitive spectrophotometric procedures for determination of trimipramine in tablet dosage form. Methods: The methods were based on the interaction of trimipramine as n-electron donor with the ο-acceptor, iodine and various π-acceptors, namely: chloranil (CH), ...

  6. Change of notch impact strength depending on radiation dose and test temperature

    Directory of Open Access Journals (Sweden)

    Martin Bednarik

    2017-01-01

    Full Text Available The main purpose of this paper has been determine the effect of radiation crosslinking on the notch impact strength of polyamides filled with fiberglass. These properties were examined in dependence on the dosage of the ionizing beta radiation (non-irradiated samples and those irradiated by dosage 66 and 132 kGy were compared and on the test temperature (23–150 °C.

  7. Immune response gene control of collagen reactivity in man: collagen unresponsiveness in HLA-DR4 negative nonresponders is due to the presence of T-dependent suppressive influences

    International Nuclear Information System (INIS)

    Solinger, A.M.; Stobo, J.D.

    1982-01-01

    To determine whether the failure to detect collagen reactivity in nonresponders represents an absence of collagen-reactive T cells or a preponderance of suppressive influences, the peripheral blood mononuclear cells from HLA-DR4 - individuals were subjected to three procedures capable of separating suppressive influences from LIF-secreting cells; irradiation (1000 rad), discontinuous gradient fractionation, and cytolysis with the monoclonal antibody OKT 8. Each procedure resulted in the specific appearance of reactivity to collagen, which was identical to that seen in HLA-DR4 + individuals with regard to its cellular requirements and antigenic specificity. Addition of unresponsive (i.e., nonirradiated or low-density T cells) to responsive (i.e., irradiated or high-density T cells) autologous populations resulted in specific suppression of collagen reactivity. Radiation-sensitive suppressive influences could not be detected in HLA-DR4 + collagen responders.These studies indicate that the expression of T-dependent reactivity to collagen in man reflects the net influence of collage-reactive vs collagen-suppressive T cells. Moreover, it is the influence of HLA-D-linked genes on the development of suppressive influences rather than on the development of collagen-reactive, LIF-secreting T cells that serves to distinguish HLA-DR4 + collagen responders from HLA-DR4 - collagen nonresponders

  8. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption

    DEFF Research Database (Denmark)

    Beck, Halfdan; Nähse-Kumpf, Viola; Larsen, Marie Sofie Yoo

    2012-01-01

    Activation of oncogenes or inhibition of WEE1 kinase deregulates Cyclin-dependent kinase (CDK) activity and leads to replication stress, however, the underlying mechanism is not understood. We now show that elevation of CDK activity by inhibiting WEE1 kinase rapidly increases initiation of replic......Activation of oncogenes or inhibition of WEE1 kinase deregulates Cyclin-dependent kinase (CDK) activity and leads to replication stress, however, the underlying mechanism is not understood. We now show that elevation of CDK activity by inhibiting WEE1 kinase rapidly increases initiation...... of replication. This leads to nucleotide shortage and reduces replication fork speed, which is followed by SLX4/MUS81-mediated DNA double-strand breakage. Fork speed is normalized and DNA double-strand break (DSB) formation is suppressed when CDT1, a key factor for replication initiation, is depleted...

  9. protVirt: protein dosage simulation by spectrometry assisting Biochemistry practical class

    Directory of Open Access Journals (Sweden)

    Gabriel Gerber Hornink

    2016-07-01

    Full Text Available The practical classes in the teaching of biochemistry could provide great contributions to the process of teaching and learning, and the understanding of these by students depend on, generally,  previous concepts about the experiment and procedures performed. It is presented in this paper the educational software protVirt, which could be used as a pedagogical innovation in the method of practical classes involving dosage of proteins, focusing on the development of skills for understanding the activities. The software was developed in Adobe Flash, with the possibility of online or offline use. Despite the possibilities of using protVirt in various modalities of education, highlights the use in online courses, in which students develop, commonly, the practical class without the teacher centers, accompanied by monitors and tutors.

  10. Prediction of dosage-based parameters from the puff dispersion of airborne materials in urban environments using the CFD-RANS methodology

    Science.gov (United States)

    Efthimiou, G. C.; Andronopoulos, S.; Bartzis, J. G.

    2018-02-01

    One of the key issues of recent research on the dispersion inside complex urban environments is the ability to predict dosage-based parameters from the puff release of an airborne material from a point source in the atmospheric boundary layer inside the built-up area. The present work addresses the question of whether the computational fluid dynamics (CFD)-Reynolds-averaged Navier-Stokes (RANS) methodology can be used to predict ensemble-average dosage-based parameters that are related with the puff dispersion. RANS simulations with the ADREA-HF code were, therefore, performed, where a single puff was released in each case. The present method is validated against the data sets from two wind-tunnel experiments. In each experiment, more than 200 puffs were released from which ensemble-averaged dosage-based parameters were calculated and compared to the model's predictions. The performance of the model was evaluated using scatter plots and three validation metrics: fractional bias, normalized mean square error, and factor of two. The model presented a better performance for the temporal parameters (i.e., ensemble-average times of puff arrival, peak, leaving, duration, ascent, and descent) than for the ensemble-average dosage and peak concentration. The majority of the obtained values of validation metrics were inside established acceptance limits. Based on the obtained model performance indices, the CFD-RANS methodology as implemented in the code ADREA-HF is able to predict the ensemble-average temporal quantities related to transient emissions of airborne material in urban areas within the range of the model performance acceptance criteria established in the literature. The CFD-RANS methodology as implemented in the code ADREA-HF is also able to predict the ensemble-average dosage, but the dosage results should be treated with some caution; as in one case, the observed ensemble-average dosage was under-estimated slightly more than the acceptance criteria. Ensemble

  11. Measurement of the jet radius and transverse momentum dependence of inclusive jet suppression in lead-lead collisions at $\\sqrt{s_{NN}}$ = 2.76 TeV with the ATLAS detector

    CERN Document Server

    Aad, Georges; Abdallah, Jalal; Abdel Khalek, Samah; Abdelalim, Ahmed Ali; Abdinov, Ovsat; Abi, Babak; Abolins, Maris; AbouZeid, Ossama; Abramowicz, Halina; Abreu, Henso; Acerbi, Emilio; Acharya, Bobby Samir; Adamczyk, Leszek; Adams, David; Addy, Tetteh; Adelman, Jahred; Adomeit, Stefanie; Adragna, Paolo; Adye, Tim; Aefsky, Scott; Aguilar-Saavedra, Juan Antonio; Agustoni, Marco; Aharrouche, Mohamed; Ahlen, Steven; Ahles, Florian; Ahmad, Ashfaq; Ahsan, Mahsana; Aielli, Giulio; Akdogan, Taylan; Åkesson, Torsten Paul Ake; Akimoto, Ginga; Akimov, Andrei; Alam, Mohammad; Alam, Muhammad Aftab; Albert, Justin; Albrand, Solveig; Aleksa, Martin; Aleksandrov, Igor; Alessandria, Franco; Alexa, Calin; Alexander, Gideon; Alexandre, Gauthier; Alexopoulos, Theodoros; Alhroob, Muhammad; Aliev, Malik; Alimonti, Gianluca; Alison, John; Allbrooke, Benedict; Allport, Phillip; Allwood-Spiers, Sarah; Almond, John; Aloisio, Alberto; Alon, Raz; Alonso, Alejandro; Alvarez Gonzalez, Barbara; Alviggi, Mariagrazia; Amako, Katsuya; Amelung, Christoph; Ammosov, Vladimir; Amorim, Antonio; Amram, Nir; Anastopoulos, Christos; Ancu, Lucian Stefan; Andari, Nansi; Andeen, Timothy; Anders, Christoph Falk; Anders, Gabriel; Anderson, Kelby; Andreazza, Attilio; Andrei, George Victor; Anduaga, Xabier; Anger, Philipp; Angerami, Aaron; Anghinolfi, Francis; Anisenkov, Alexey; Anjos, Nuno; Annovi, Alberto; Antonaki, Ariadni; Antonelli, Mario; Antonov, Alexey; Antos, Jaroslav; Anulli, Fabio; Aoun, Sahar; Aperio Bella, Ludovica; Apolle, Rudi; Arabidze, Giorgi; Aracena, Ignacio; Arai, Yasuo; Arce, Ayana; Arfaoui, Samir; Arguin, Jean-Francois; Arik, Engin; Arik, Metin; Armbruster, Aaron James; Arnaez, Olivier; Arnal, Vanessa; Arnault, Christian; Artamonov, Andrei; Artoni, Giacomo; Arutinov, David; Asai, Shoji; Asfandiyarov, Ruslan; Ask, Stefan; Åsman, Barbro; Asquith, Lily; Assamagan, Ketevi; Astbury, Alan; Aubert, Bernard; Auge, Etienne; Augsten, Kamil; Aurousseau, Mathieu; Avolio, Giuseppe; Avramidou, Rachel Maria; Axen, David; Azuelos, Georges; Azuma, Yuya; Baak, Max; Baccaglioni, Giuseppe; Bacci, Cesare; Bach, Andre; Bachacou, Henri; Bachas, Konstantinos; Backes, Moritz; Backhaus, Malte; Badescu, Elisabeta; Bagnaia, Paolo; Bahinipati, Seema; Bai, Yu; Bailey, David; Bain, Travis; Baines, John; Baker, Oliver Keith; Baker, Mark; Baker, Sarah; Banas, Elzbieta; Banerjee, Piyali; Banerjee, Swagato; Banfi, Danilo; Bangert, Andrea Michelle; Bansal, Vikas; Bansil, Hardeep Singh; Barak, Liron; Baranov, Sergei; Barbaro Galtieri, Angela; Barber, Tom; Barberio, Elisabetta Luigia; Barberis, Dario; Barbero, Marlon; Bardin, Dmitri; Barillari, Teresa; Barisonzi, Marcello; Barklow, Timothy; Barlow, Nick; Barnett, Bruce; Barnett, Michael; Baroncelli, Antonio; Barone, Gaetano; Barr, Alan; Barreiro, Fernando; Barreiro Guimarães da Costa, João; Barrillon, Pierre; Bartoldus, Rainer; Barton, Adam Edward; Bartsch, Valeria; Bates, Richard; Batkova, Lucia; Batley, Richard; Battaglia, Andreas; Battistin, Michele; Bauer, Florian; Bawa, Harinder Singh; Beale, Steven; Beau, Tristan; Beauchemin, Pierre-Hugues; Beccherle, Roberto; Bechtle, Philip; Beck, Hans Peter; Becker, Anne Kathrin; Becker, Sebastian; Beckingham, Matthew; Becks, Karl-Heinz; Beddall, Andrew; Beddall, Ayda; Bedikian, Sourpouhi; Bednyakov, Vadim; Bee, Christopher; Begel, Michael; Behar Harpaz, Silvia; Beimforde, Michael; Belanger-Champagne, Camille; Bell, Paul; Bell, William; Bella, Gideon; Bellagamba, Lorenzo; Bellina, Francesco; Bellomo, Massimiliano; Belloni, Alberto; Beloborodova, Olga; Belotskiy, Konstantin; Beltramello, Olga; Benary, Odette; Benchekroun, Driss; Bendtz, Katarina; Benekos, Nektarios; Benhammou, Yan; Benhar Noccioli, Eleonora; Benitez Garcia, Jorge-Armando; Benjamin, Douglas; Benoit, Mathieu; Bensinger, James; Benslama, Kamal; Bentvelsen, Stan; Berge, David; Bergeaas Kuutmann, Elin; Berger, Nicolas; Berghaus, Frank; Berglund, Elina; Beringer, Jürg; Bernat, Pauline; Bernhard, Ralf; Bernius, Catrin; Berry, Tracey; Bertella, Claudia; Bertin, Antonio; Bertolucci, Federico; Besana, Maria Ilaria; Besjes, Geert-Jan; Besson, Nathalie; Bethke, Siegfried; Bhimji, Wahid; Bianchi, Riccardo-Maria; Bianco, Michele; Biebel, Otmar; Bieniek, Stephen Paul; Bierwagen, Katharina; Biesiada, Jed; Biglietti, Michela; Bilokon, Halina; Bindi, Marcello; Binet, Sebastien; Bingul, Ahmet; Bini, Cesare; Biscarat, Catherine; Bitenc, Urban; Black, Kevin; Blair, Robert; Blanchard, Jean-Baptiste; Blanchot, Georges; Blazek, Tomas; Blocker, Craig; Blocki, Jacek; Blondel, Alain; Blum, Walter; Blumenschein, Ulrike; Bobbink, Gerjan; Bobrovnikov, Victor; Bocchetta, Simona Serena; Bocci, Andrea; Boddy, Christopher Richard; Boehler, Michael; Boek, Jennifer; Boelaert, Nele; Bogaerts, Joannes Andreas; Bogdanchikov, Alexander; Bogouch, Andrei; Bohm, Christian; Bohm, Jan; Boisvert, Veronique; Bold, Tomasz; Boldea, Venera; Bolnet, Nayanka Myriam; Bomben, Marco; Bona, Marcella; Boonekamp, Maarten; Booth, Chris; Bordoni, Stefania; Borer, Claudia; Borisov, Anatoly; Borissov, Guennadi; Borjanovic, Iris; Borri, Marcello; Borroni, Sara; Bortolotto, Valerio; Bos, Kors; Boscherini, Davide; Bosman, Martine; Boterenbrood, Hendrik; Botterill, David; Bouchami, Jihene; Boudreau, Joseph; Bouhova-Thacker, Evelina Vassileva; Boumediene, Djamel Eddine; Bourdarios, Claire; Bousson, Nicolas; Boveia, Antonio; Boyd, James; Boyko, Igor; Bozovic-Jelisavcic, Ivanka; Bracinik, Juraj; Branchini, Paolo; Brandt, Andrew; Brandt, Gerhard; Brandt, Oleg; Bratzler, Uwe; Brau, Benjamin; Brau, James; Braun, Helmut; Brazzale, Simone Federico; Brelier, Bertrand; Bremer, Johan; Brendlinger, Kurt; Brenner, Richard; Bressler, Shikma; Britton, Dave; Brochu, Frederic; Brock, Ian; Brock, Raymond; Brodet, Eyal; Broggi, Francesco; Bromberg, Carl; Bronner, Johanna; Brooijmans, Gustaaf; Brooks, Timothy; Brooks, William; Brown, Gareth; Brown, Heather; Bruckman de Renstrom, Pawel; Bruncko, Dusan; Bruneliere, Renaud; Brunet, Sylvie; Bruni, Alessia; Bruni, Graziano; Bruschi, Marco; Buanes, Trygve; Buat, Quentin; Bucci, Francesca; Buchanan, James; Buchholz, Peter; Buckingham, Ryan; Buckley, Andrew; Buda, Stelian Ioan; Budagov, Ioulian; Budick, Burton; Büscher, Volker; Bugge, Lars; Bulekov, Oleg; Bundock, Aaron Colin; Bunse, Moritz; Buran, Torleiv; Burckhart, Helfried; Burdin, Sergey; Burgess, Thomas; Burke, Stephen; Busato, Emmanuel; Bussey, Peter; Buszello, Claus-Peter; Butler, Bart; Butler, John; Buttar, Craig; Butterworth, Jonathan; Buttinger, William; Cabrera Urbán, Susana; Caforio, Davide; Cakir, Orhan; Calafiura, Paolo; Calderini, Giovanni; Calfayan, Philippe; Calkins, Robert; Caloba, Luiz; Caloi, Rita; Calvet, David; Calvet, Samuel; Camacho Toro, Reina; Camarri, Paolo; Cameron, David; Caminada, Lea Michaela; Campana, Simone; Campanelli, Mario; Canale, Vincenzo; Canelli, Florencia; Canepa, Anadi; Cantero, Josu; Cantrill, Robert; Capasso, Luciano; Capeans Garrido, Maria Del Mar; Caprini, Irinel; Caprini, Mihai; Capriotti, Daniele; Capua, Marcella; Caputo, Regina; Cardarelli, Roberto; Carli, Tancredi; Carlino, Gianpaolo; Carminati, Leonardo; Caron, Bryan; Caron, Sascha; Carquin, Edson; Carrillo Montoya, German D; Carter, Antony; Carter, Janet; Carvalho, João; Casadei, Diego; Casado, Maria Pilar; Cascella, Michele; Caso, Carlo; Castaneda Hernandez, Alfredo Martin; Castaneda-Miranda, Elizabeth; Castillo Gimenez, Victoria; Castro, Nuno Filipe; Cataldi, Gabriella; Catastini, Pierluigi; Catinaccio, Andrea; Catmore, James; Cattai, Ariella; Cattani, Giordano; Caughron, Seth; Cavalleri, Pietro; Cavalli, Donatella; Cavalli-Sforza, Matteo; Cavasinni, Vincenzo; Ceradini, Filippo; Santiago Cerqueira, Augusto; Cerri, Alessandro; Cerrito, Lucio; Cerutti, Fabio; Cetin, Serkant Ali; Chafaq, Aziz; Chakraborty, Dhiman; Chalupkova, Ina; Chan, Kevin; Chapleau, Bertrand; Chapman, John Derek; Chapman, John Wehrley; Chareyre, Eve; Charlton, Dave; Chavda, Vikash; Chavez Barajas, Carlos Alberto; Cheatham, Susan; Chekanov, Sergei; Chekulaev, Sergey; Chelkov, Gueorgui; Chelstowska, Magda Anna; Chen, Chunhui; Chen, Hucheng; Chen, Shenjian; Chen, Xin; Chen, Yujiao; Cheplakov, Alexander; Cherkaoui El Moursli, Rajaa; Chernyatin, Valeriy; Cheu, Elliott; Cheung, Sing-Leung; Chevalier, Laurent; Chiefari, Giovanni; Chikovani, Leila; Childers, John Taylor; Chilingarov, Alexandre; Chiodini, Gabriele; Chisholm, Andrew; Chislett, Rebecca Thalatta; Chitan, Adrian; Chizhov, Mihail; Choudalakis, Georgios; Chouridou, Sofia; Christidi, Illectra-Athanasia; Christov, Asen; Chromek-Burckhart, Doris; Chu, Ming-Lee; Chudoba, Jiri; Ciapetti, Guido; Ciftci, Abbas Kenan; Ciftci, Rena; Cinca, Diane; Cindro, Vladimir; Ciocca, Claudia; Ciocio, Alessandra; Cirilli, Manuela; Cirkovic, Predrag; Citterio, Mauro; Ciubancan, Mihai; Clark, Allan G; Clark, Philip James; Clarke, Robert; Cleland, Bill; Clemens, Jean-Claude; Clement, Benoit; Clement, Christophe; Coadou, Yann; Cobal, Marina; Coccaro, Andrea; Cochran, James H; Cogan, Joshua Godfrey; Coggeshall, James; Cogneras, Eric; Colas, Jacques; Colijn, Auke-Pieter; Collins, Neil; Collins-Tooth, Christopher; Collot, Johann; Colombo, Tommaso; Colon, German; Conde Muiño, Patricia; Coniavitis, Elias; Conidi, Maria Chiara; Consonni, Sofia Maria; Consorti, Valerio; Constantinescu, Serban; Conta, Claudio; Conti, Geraldine; Conventi, Francesco; Cooke, Mark; Cooper, Ben; Cooper-Sarkar, Amanda; Copic, Katherine; Cornelissen, Thijs; Corradi, Massimo; Corriveau, Francois; Cortes-Gonzalez, Arely; Cortiana, Giorgio; Costa, Giuseppe; Costa, María José; Costanzo, Davide; Costin, Tudor; Côté, David; Courneyea, Lorraine; Cowan, Glen; Cowden, Christopher; Cox, Brian; Cranmer, Kyle; Crescioli, Francesco; Cristinziani, Markus; Crosetti, Giovanni; Crupi, Roberto; Crépé-Renaudin, Sabine; Cuciuc, Constantin-Mihai; Cuenca Almenar, Cristóbal; Cuhadar Donszelmann, Tulay; Curatolo, Maria; Curtis, Chris; Cuthbert, Cameron; Cwetanski, Peter; Czirr, Hendrik; Czodrowski, Patrick; Czyczula, Zofia; D'Auria, Saverio; D'Onofrio, Monica; D'Orazio, Alessia; Da Cunha Sargedas De Sousa, Mario Jose; Da Via, Cinzia; Dabrowski, Wladyslaw; Dafinca, Alexandru; Dai, Tiesheng; Dallapiccola, Carlo; Dam, Mogens; Dameri, Mauro; Damiani, Daniel; Danielsson, Hans Olof; Dao, Valerio; Darbo, Giovanni; Darlea, Georgiana Lavinia; Davey, Will; Davidek, Tomas; Davidson, Nadia; Davidson, Ruth; Davies, Eleanor; Davies, Merlin; Davison, Adam; Davygora, Yuriy; Dawe, Edmund; Dawson, Ian; Daya-Ishmukhametova, Rozmin; De, Kaushik; de Asmundis, Riccardo; De Castro, Stefano; De Cecco, Sandro; de Graat, Julien; De Groot, Nicolo; de Jong, Paul; De La Taille, Christophe; De la Torre, Hector; De Lorenzi, Francesco; de Mora, Lee; De Nooij, Lucie; De Pedis, Daniele; De Salvo, Alessandro; De Sanctis, Umberto; De Santo, Antonella; De Vivie De Regie, Jean-Baptiste; De Zorzi, Guido; Dearnaley, William James; Debbe, Ramiro; Debenedetti, Chiara; Dechenaux, Benjamin; Dedovich, Dmitri; Degenhardt, James; Del Papa, Carlo; Del Peso, Jose; Del Prete, Tarcisio; Delemontex, Thomas; Deliyergiyev, Maksym; Dell'Acqua, Andrea; Dell'Asta, Lidia; Della Pietra, Massimo; della Volpe, Domenico; Delmastro, Marco; Delsart, Pierre-Antoine; Deluca, Carolina; Demers, Sarah; Demichev, Mikhail; Demirkoz, Bilge; Deng, Jianrong; Denisov, Sergey; Derendarz, Dominik; Derkaoui, Jamal Eddine; Derue, Frederic; Dervan, Paul; Desch, Klaus Kurt; Devetak, Erik; Deviveiros, Pier-Olivier; Dewhurst, Alastair; DeWilde, Burton; Dhaliwal, Saminder; Dhullipudi, Ramasudhakar; Di Ciaccio, Anna; Di Ciaccio, Lucia; Di Girolamo, Alessandro; Di Girolamo, Beniamino; Di Luise, Silvestro; Di Mattia, Alessandro; Di Micco, Biagio; Di Nardo, Roberto; Di Simone, Andrea; Di Sipio, Riccardo; Diaz, Marco Aurelio; Diehl, Edward; Dietrich, Janet; Dietzsch, Thorsten; Diglio, Sara; Dindar Yagci, Kamile; Dingfelder, Jochen; Dinut, Florin; Dionisi, Carlo; Dita, Petre; Dita, Sanda; Dittus, Fridolin; Djama, Fares; Djobava, Tamar; Barros do Vale, Maria Aline; Do Valle Wemans, André; Doan, Thi Kieu Oanh; Dobbs, Matt; Dobinson, Robert; Dobos, Daniel; Dobson, Ellie; Dodd, Jeremy; Doglioni, Caterina; Doherty, Tom; Doi, Yoshikuni; Dolejsi, Jiri; Dolenc, Irena; Dolezal, Zdenek; Dolgoshein, Boris; Dohmae, Takeshi; Donadelli, Marisilvia; Donini, Julien; Dopke, Jens; Doria, Alessandra; Dos Anjos, Andre; Dotti, Andrea; Dova, Maria-Teresa; Doxiadis, Alexander; Doyle, Tony; Dris, Manolis; Dubbert, Jörg; Dube, Sourabh; Duchovni, Ehud; Duckeck, Guenter; Dudarev, Alexey; Dudziak, Fanny; Dührssen, Michael; Duerdoth, Ian; Duflot, Laurent; Dufour, Marc-Andre; Dunford, Monica; Duran Yildiz, Hatice; Duxfield, Robert; Dwuznik, Michal; Dydak, Friedrich; Düren, Michael; Ebke, Johannes; Eckweiler, Sebastian; Edmonds, Keith; Edwards, Clive; Edwards, Nicholas Charles; Ehrenfeld, Wolfgang; Eifert, Till; Eigen, Gerald; Einsweiler, Kevin; Eisenhandler, Eric; Ekelof, Tord; El Kacimi, Mohamed; Ellert, Mattias; Elles, Sabine; Ellinghaus, Frank; Ellis, Katherine; Ellis, Nicolas; Elmsheuser, Johannes; Elsing, Markus; Emeliyanov, Dmitry; Engelmann, Roderich; Engl, Albert; Epp, Brigitte; Eppig, Andrew; Erdmann, Johannes; Ereditato, Antonio; Eriksson, Daniel; Ernst, Jesse; Ernst, Michael; Ernwein, Jean; Errede, Deborah; Errede, Steven; Ertel, Eugen; Escalier, Marc; Esch, Hendrik; Escobar, Carlos; Espinal Curull, Xavier; Esposito, Bellisario; Etienne, Francois; Etienvre, Anne-Isabelle; Etzion, Erez; Evangelakou, Despoina; Evans, Hal; Fabbri, Laura; Fabre, Caroline; Fakhrutdinov, Rinat; Falciano, Speranza; Fang, Yaquan; Fanti, Marcello; Farbin, Amir; Farilla, Addolorata; Farley, Jason; Farooque, Trisha; Farrell, Steven; Farrington, Sinead; Farthouat, Philippe; Fassnacht, Patrick; Fassouliotis, Dimitrios; Fatholahzadeh, Baharak; Favareto, Andrea; Fayard, Louis; Fazio, Salvatore; Febbraro, Renato; Federic, Pavol; Fedin, Oleg; Fedorko, Wojciech; Fehling-Kaschek, Mirjam; Feligioni, Lorenzo; Fellmann, Denis; Feng, Cunfeng; Feng, Eric; Fenyuk, Alexander; Ferencei, Jozef; Fernando, Waruna; Ferrag, Samir; Ferrando, James; Ferrara, Valentina; Ferrari, Arnaud; Ferrari, Pamela; Ferrari, Roberto; Ferreira de Lima, Danilo Enoque; Ferrer, Antonio; Ferrere, Didier; Ferretti, Claudio; Ferretto Parodi, Andrea; Fiascaris, Maria; Fiedler, Frank; Filipčič, Andrej; Filthaut, Frank; Fincke-Keeler, Margret; Fiolhais, Miguel; Fiorini, Luca; Firan, Ana; Fischer, Gordon; Fisher, Matthew; Flechl, Martin; Fleck, Ivor; Fleckner, Johanna; Fleischmann, Philipp; Fleischmann, Sebastian; Flick, Tobias; Floderus, Anders; Flores Castillo, Luis; Flowerdew, Michael; Fonseca Martin, Teresa; Formica, Andrea; Forti, Alessandra; Fortin, Dominique; Fournier, Daniel; Fox, Harald; Francavilla, Paolo; Franchino, Silvia; Francis, David; Frank, Tal; Franz, Sebastien; Fraternali, Marco; Fratina, Sasa; French, Sky; Friedrich, Conrad; Friedrich, Felix; Froeschl, Robert; Froidevaux, Daniel; Frost, James; Fukunaga, Chikara; Fullana Torregrosa, Esteban; Fulsom, Bryan Gregory; Fuster, Juan; Gabaldon, Carolina; Gabizon, Ofir; Gadfort, Thomas; Gadomski, Szymon; Gagliardi, Guido; Gagnon, Pauline; Galea, Cristina; Gallas, Elizabeth; Gallo, Valentina Santina; Gallop, Bruce; Gallus, Petr; Gan, KK; Gao, Yongsheng; Gaponenko, Andrei; Garberson, Ford; Garcia-Sciveres, Maurice; García, Carmen; García Navarro, José Enrique; Gardner, Robert; Garelli, Nicoletta; Garitaonandia, Hegoi; Garonne, Vincent; Garvey, John; Gatti, Claudio; Gaudio, Gabriella; Gaur, Bakul; Gauthier, Lea; Gauzzi, Paolo; Gavrilenko, Igor; Gay, Colin; Gaycken, Goetz; Gazis, Evangelos; Ge, Peng; Gecse, Zoltan; Gee, Norman; Geerts, Daniël Alphonsus Adrianus; Geich-Gimbel, Christoph; Gellerstedt, Karl; Gemme, Claudia; Gemmell, Alistair; Genest, Marie-Hélène; Gentile, Simonetta; George, Matthias; George, Simon; Gerlach, Peter; Gershon, Avi; Geweniger, Christoph; Ghazlane, Hamid; Ghodbane, Nabil; Giacobbe, Benedetto; Giagu, Stefano; Giakoumopoulou, Victoria; Giangiobbe, Vincent; Gianotti, Fabiola; Gibbard, Bruce; Gibson, Adam; Gibson, Stephen; Gillberg, Dag; Gillman, Tony; Gingrich, Douglas; Ginzburg, Jonatan; Giokaris, Nikos; Giordani, MarioPaolo; Giordano, Raffaele; Giorgi, Francesco Michelangelo; Giovannini, Paola; Giraud, Pierre-Francois; Giugni, Danilo; Giunta, Michele; Giusti, Paolo; Gjelsten, Børge Kile; Gladilin, Leonid; Glasman, Claudia; Glatzer, Julian; Glazov, Alexandre; Glitza, Karl-Walter; Glonti, George; Goddard, Jack Robert; Godfrey, Jennifer; Godlewski, Jan; Goebel, Martin; Göpfert, Thomas; Goeringer, Christian; Gössling, Claus; Goldfarb, Steven; Golling, Tobias; Gomes, Agostinho; Gomez Fajardo, Luz Stella; Gonçalo, Ricardo; Goncalves Pinto Firmino Da Costa, Joao; Gonella, Laura; Gonzalez, Saul; González de la Hoz, Santiago; Gonzalez Parra, Garoe; Gonzalez Silva, Laura; Gonzalez-Sevilla, Sergio; Goodson, Jeremiah Jet; Goossens, Luc; Gorbounov, Petr Andreevich; Gordon, Howard; Gorelov, Igor; Gorfine, Grant; Gorini, Benedetto; Gorini, Edoardo; Gorišek, Andrej; Gornicki, Edward; Gosdzik, Bjoern; Goshaw, Alfred; Gosselink, Martijn; Gostkin, Mikhail Ivanovitch; Gough Eschrich, Ivo; Gouighri, Mohamed; Goujdami, Driss; Goulette, Marc Phillippe; Goussiou, Anna; Goy, Corinne; Gozpinar, Serdar; Grabowska-Bold, Iwona; Grafström, Per; Grahn, Karl-Johan; Grancagnolo, Francesco; Grancagnolo, Sergio; Grassi, Valerio; Gratchev, Vadim; Grau, Nathan; Gray, Heather; Gray, Julia Ann; Graziani, Enrico; Grebenyuk, Oleg; Greenshaw, Timothy; Greenwood, Zeno Dixon; Gregersen, Kristian; Gregor, Ingrid-Maria; Grenier, Philippe; Griffiths, Justin; Grigalashvili, Nugzar; Grillo, Alexander; Grinstein, Sebastian; Grishkevich, Yaroslav; Grivaz, Jean-Francois; Gross, Eilam; Grosse-Knetter, Joern; Groth-Jensen, Jacob; Grybel, Kai; Guest, Daniel; Guicheney, Christophe; Guida, Angelo; Guindon, Stefan; Gul, Umar; Guler, Hulya; Gunther, Jaroslav; Guo, Bin; Guo, Jun; Gutierrez, Phillip; Guttman, Nir; Gutzwiller, Olivier; Guyot, Claude; Gwenlan, Claire; Gwilliam, Carl; Haas, Andy; Haas, Stefan; Haber, Carl; Hadavand, Haleh Khani; Hadley, David; Haefner, Petra; Hahn, Ferdinand; Haider, Stefan; Hajduk, Zbigniew; Hakobyan, Hrachya; Hall, David; Haller, Johannes; Hamacher, Klaus; Hamal, Petr; Hamer, Matthias; Hamilton, Andrew; Hamilton, Samuel; Han, Liang; Hanagaki, Kazunori; Hanawa, Keita; Hance, Michael; Handel, Carsten; Hanke, Paul; Hansen, John Renner; Hansen, Jørgen Beck; Hansen, Jorn Dines; Hansen, Peter Henrik; Hansson, Per; Hara, Kazuhiko; Hare, Gabriel; Harenberg, Torsten; Harkusha, Siarhei; Harper, Devin; Harrington, Robert; Harris, Orin; Hartert, Jochen; Hartjes, Fred; Haruyama, Tomiyoshi; Harvey, Alex; Hasegawa, Satoshi; Hasegawa, Yoji; Hassani, Samira; Haug, Sigve; Hauschild, Michael; Hauser, Reiner; Havranek, Miroslav; Hawkes, Christopher; Hawkings, Richard John; Hawkins, Anthony David; Hawkins, Donovan; Hayakawa, Takashi; Hayashi, Takayasu; Hayden, Daniel; Hays, Chris; Hayward, Helen; Haywood, Stephen; He, Mao; Head, Simon; Hedberg, Vincent; Heelan, Louise; Heim, Sarah; Heinemann, Beate; Heisterkamp, Simon; Helary, Louis; Heller, Claudio; Heller, Matthieu; Hellman, Sten; Hellmich, Dennis; Helsens, Clement; Henderson, Robert; Henke, Michael; Henrichs, Anna; Henriques Correia, Ana Maria; Henrot-Versille, Sophie; Hensel, Carsten; Henß, Tobias; Medina Hernandez, Carlos; Hernández Jiménez, Yesenia; Herrberg, Ruth; Herten, Gregor; Hertenberger, Ralf; Hervas, Luis; Hesketh, Gavin Grant; Hessey, Nigel; Higón-Rodriguez, Emilio; Hill, John; Hiller, Karl Heinz; Hillert, Sonja; Hillier, Stephen; Hinchliffe, Ian; Hines, Elizabeth; Hirose, Minoru; Hirsch, Florian; Hirschbuehl, Dominic; Hobbs, John; Hod, Noam; Hodgkinson, Mark; Hodgson, Paul; Hoecker, Andreas; Hoeferkamp, Martin; Hoffman, Julia; Hoffmann, Dirk; Hohlfeld, Marc; Holder, Martin; Holmgren, Sven-Olof; Holy, Tomas; Holzbauer, Jenny; Hong, Tae Min; Hooft van Huysduynen, Loek; Horn, Claus; Horner, Stephan; Hostachy, Jean-Yves; Hou, Suen; Hoummada, Abdeslam; Howard, Jacob; Howarth, James; Hristova, Ivana; Hrivnac, Julius; Hryn'ova, Tetiana; Hsu, Pai-hsien Jennifer; Hsu, Shih-Chieh; Hubacek, Zdenek; Hubaut, Fabrice; Huegging, Fabian; Huettmann, Antje; Huffman, Todd Brian; Hughes, Emlyn; Hughes, Gareth; Huhtinen, Mika; Hurwitz, Martina; Husemann, Ulrich; Huseynov, Nazim; Huston, Joey; Huth, John; Iacobucci, Giuseppe; Iakovidis, Georgios; Ibbotson, Michael; Ibragimov, Iskander; Iconomidou-Fayard, Lydia; Idarraga, John; Iengo, Paolo; Igonkina, Olga; Ikegami, Yoichi; Ikeno, Masahiro; Iliadis, Dimitrios; Ilic, Nikolina; Ince, Tayfun; Inigo-Golfin, Joaquin; Ioannou, Pavlos; Iodice, Mauro; Iordanidou, Kalliopi; Ippolito, Valerio; Irles Quiles, Adrian; Isaksson, Charlie; Ishino, Masaya; Ishitsuka, Masaki; Ishmukhametov, Renat; Issever, Cigdem; Istin, Serhat; Ivashin, Anton; Iwanski, Wieslaw; Iwasaki, Hiroyuki; Izen, Joseph; Izzo, Vincenzo; Jackson, Brett; Jackson, John; Jackson, Paul; Jaekel, Martin; Jain, Vivek; Jakobs, Karl; Jakobsen, Sune; Jakoubek, Tomas; Jakubek, Jan; Jana, Dilip; Jansen, Eric; Jansen, Hendrik; Jantsch, Andreas; Janus, Michel; Jarlskog, Göran; Jeanty, Laura; Jen-La Plante, Imai; Jenni, Peter; Jeremie, Andrea; Jež, Pavel; Jézéquel, Stéphane; Jha, Manoj Kumar; Ji, Haoshuang; Ji, Weina; Jia, Jiangyong; Jiang, Yi; Jimenez Belenguer, Marcos; Jin, Shan; Jinnouchi, Osamu; Joergensen, Morten Dam; Joffe, David; Johansen, Marianne; Johansson, Erik; Johansson, Per; Johnert, Sebastian; Johns, Kenneth; Jon-And, Kerstin; Jones, Graham; Jones, Roger; Jones, Tim; Joram, Christian; Jorge, Pedro; Joshi, Kiran Daniel; Jovicevic, Jelena; Jovin, Tatjana; Ju, Xiangyang; Jung, Christian; Jungst, Ralph Markus; Juranek, Vojtech; Jussel, Patrick; Juste Rozas, Aurelio; Kabana, Sonja; Kaci, Mohammed; Kaczmarska, Anna; Kadlecik, Peter; Kado, Marumi; Kagan, Harris; Kagan, Michael; Kajomovitz, Enrique; Kalinin, Sergey; Kalinovskaya, Lidia; Kama, Sami; Kanaya, Naoko; Kaneda, Michiru; Kaneti, Steven; Kanno, Takayuki; Kantserov, Vadim; Kanzaki, Junichi; Kaplan, Benjamin; Kapliy, Anton; Kaplon, Jan; Kar, Deepak; Karagounis, Michael; Karakostas, Konstantinos; Karnevskiy, Mikhail; Kartvelishvili, Vakhtang; Karyukhin, Andrey; Kashif, Lashkar; Kasieczka, Gregor; Kass, Richard; Kastanas, Alex; Kataoka, Mayuko; Kataoka, Yousuke; Katsoufis, Elias; Katzy, Judith; Kaushik, Venkatesh; Kawagoe, Kiyotomo; Kawamoto, Tatsuo; Kawamura, Gen; Kayl, Manuel; Kazanin, Vassili; Kazarinov, Makhail; Keeler, Richard; Kehoe, Robert; Keil, Markus; Kekelidze, George; Keller, John; Kenyon, Mike; Kepka, Oldrich; Kerschen, Nicolas; Kerševan, Borut Paul; Kersten, Susanne; Kessoku, Kohei; Keung, Justin; Khalil-zada, Farkhad; Khandanyan, Hovhannes; Khanov, Alexander; Kharchenko, Dmitri; Khodinov, Alexander; Khomich, Andrei; Khoo, Teng Jian; Khoriauli, Gia; Khoroshilov, Andrey; Khovanskiy, Valery; Khramov, Evgeniy; Khubua, Jemal; Kim, Hyeon Jin; Kim, Shinhong; Kimura, Naoki; Kind, Oliver; King, Barry; King, Matthew; King, Robert Steven Beaufoy; Kirk, Julie; Kiryunin, Andrey; Kishimoto, Tomoe; Kisielewska, Danuta; Kittelmann, Thomas; Kladiva, Eduard; Klein, Max; Klein, Uta; Kleinknecht, Konrad; Klemetti, Miika; Klier, Amit; Klimek, Pawel; Klimentov, Alexei; Klingenberg, Reiner; Klinger, Joel Alexander; Klinkby, Esben; Klioutchnikova, Tatiana; Klok, Peter; Klous, Sander; Kluge, Eike-Erik; Kluge, Thomas; Kluit, Peter; Kluth, Stefan; Knecht, Neil; Kneringer, Emmerich; Knoops, Edith; Knue, Andrea; Ko, Byeong Rok; Kobayashi, Tomio; Kobel, Michael; Kocian, Martin; Kodys, Peter; Köneke, Karsten; König, Adriaan; Koenig, Sebastian; Köpke, Lutz; Koetsveld, Folkert; Koevesarki, Peter; Koffas, Thomas; Koffeman, Els; Kogan, Lucy Anne; Kohlmann, Simon; Kohn, Fabian; Kohout, Zdenek; Kohriki, Takashi; Koi, Tatsumi; Kolachev, Guennady; Kolanoski, Hermann; Kolesnikov, Vladimir; Koletsou, Iro; Koll, James; Kollefrath, Michael; Komar, Aston; Komori, Yuto; Kondo, Takahiko; Kono, Takanori; Kononov, Anatoly; Konoplich, Rostislav; Konstantinidis, Nikolaos; Koperny, Stefan; Korcyl, Krzysztof; Kordas, Kostantinos; Korn, Andreas; Korol, Aleksandr; Korolkov, Ilya; Korolkova, Elena; Korotkov, Vladislav; Kortner, Oliver; Kortner, Sandra; Kostyukhin, Vadim; Kotov, Sergey; Kotov, Vladislav; Kotwal, Ashutosh; Kourkoumelis, Christine; Kouskoura, Vasiliki; Koutsman, Alex; Kowalewski, Robert Victor; Kowalski, Tadeusz; Kozanecki, Witold; Kozhin, Anatoly; Kral, Vlastimil; Kramarenko, Viktor; Kramberger, Gregor; Krasny, Mieczyslaw Witold; Krasznahorkay, Attila; Kraus, James; Kraus, Jana; Kreiss, Sven; Krejci, Frantisek; Kretzschmar, Jan; Krieger, Nina; Krieger, Peter; Kroeninger, Kevin; Kroha, Hubert; Kroll, Joe; Kroseberg, Juergen; Krstic, Jelena; Kruchonak, Uladzimir; Krüger, Hans; Kruker, Tobias; Krumnack, Nils; Krumshteyn, Zinovii; Kruth, Andre; Kubota, Takashi; Kuday, Sinan; Kuehn, Susanne; Kugel, Andreas; Kuhl, Thorsten; Kuhn, Dietmar; Kukhtin, Victor; Kulchitsky, Yuri; Kuleshov, Sergey; Kummer, Christian; Kuna, Marine; Kunkle, Joshua; Kupco, Alexander; Kurashige, Hisaya; Kurata, Masakazu; Kurochkin, Yurii; Kus, Vlastimil; Kuwertz, Emma Sian; Kuze, Masahiro; Kvita, Jiri; Kwee, Regina; La Rosa, Alessandro; La Rotonda, Laura; Labarga, Luis; Labbe, Julien; Lablak, Said; Lacasta, Carlos; Lacava, Francesco; Lacker, Heiko; Lacour, Didier; Lacuesta, Vicente Ramón; Ladygin, Evgueni; Lafaye, Remi; Laforge, Bertrand; Lagouri, Theodota; Lai, Stanley; Laisne, Emmanuel; Lamanna, Massimo; Lambourne, Luke; Lampen, Caleb; Lampl, Walter; Lancon, Eric; Landgraf, Ulrich; Landon, Murrough; Lane, Jenna; Lang, Valerie Susanne; Lange, Clemens; Lankford, Andrew; Lanni, Francesco; Lantzsch, Kerstin; Laplace, Sandrine; Lapoire, Cecile; Laporte, Jean-Francois; Lari, Tommaso; Larner, Aimee; Lassnig, Mario; Laurelli, Paolo; Lavorini, Vincenzo; Lavrijsen, Wim; Laycock, Paul; Le Dortz, Olivier; Le Guirriec, Emmanuel; Le Maner, Christophe; Le Menedeu, Eve; LeCompte, Thomas; Ledroit-Guillon, Fabienne Agnes Marie; Lee, Hurng-Chun; Lee, Jason; Lee, Shih-Chang; Lee, Lawrence; Lefebvre, Michel; Legendre, Marie; Legger, Federica; Leggett, Charles; Lehmacher, Marc; Lehmann Miotto, Giovanna; Lei, Xiaowen; Leite, Marco Aurelio Lisboa; Leitner, Rupert; Lellouch, Daniel; Lemmer, Boris; Lendermann, Victor; Leney, Katharine; Lenz, Tatiana; Lenzen, Georg; Lenzi, Bruno; Leonhardt, Kathrin; Leontsinis, Stefanos; Lepold, Florian; Leroy, Claude; Lessard, Jean-Raphael; Lester, Christopher; Lester, Christopher Michael; Levêque, Jessica; Levin, Daniel; Levinson, Lorne; Lewis, Adrian; Lewis, George; Leyko, Agnieszka; Leyton, Michael; Li, Bo; Li, Haifeng; Li, Shu; Li, Xuefei; Liang, Zhijun; Liao, Hongbo; Liberti, Barbara; Lichard, Peter; Lichtnecker, Markus; Lie, Ki; Liebig, Wolfgang; Limbach, Christian; Limosani, Antonio; Limper, Maaike; Lin, Simon; Linde, Frank; Linnemann, James; Lipeles, Elliot; Lipniacka, Anna; Liss, Tony; Lissauer, David; Lister, Alison; Litke, Alan; Liu, Chuanlei; Liu, Dong; Liu, Hao; Liu, Jianbei; Liu, Lulu; Liu, Minghui; Liu, Yanwen; Livan, Michele; Livermore, Sarah; Lleres, Annick; Llorente Merino, Javier; Lloyd, Stephen; Lobodzinska, Ewelina; Loch, Peter; Lockman, William; Loddenkoetter, Thomas; Loebinger, Fred; Loginov, Andrey; Loh, Chang Wei; Lohse, Thomas; Lohwasser, Kristin; Lokajicek, Milos; Lombardo, Vincenzo Paolo; Long, Robin Eamonn; Lopes, Lourenco; Lopez Mateos, David; Lorenz, Jeanette; Lorenzo Martinez, Narei; Losada, Marta; Loscutoff, Peter; Lo Sterzo, Francesco; Losty, Michael; Lou, Xinchou; Lounis, Abdenour; Loureiro, Karina; Love, Jeremy; Love, Peter; Lowe, Andrew; Lu, Feng; Lubatti, Henry; Luci, Claudio; Lucotte, Arnaud; Ludwig, Andreas; Ludwig, Dörthe; Ludwig, Inga; Ludwig, Jens; Luehring, Frederick; Luijckx, Guy; Lukas, Wolfgang; Lumb, Debra; Luminari, Lamberto; Lund, Esben; Lund-Jensen, Bengt; Lundberg, Björn; Lundberg, Johan; Lundberg, Olof; Lundquist, Johan; Lungwitz, Matthias; Lynn, David; Lytken, Else; Ma, Hong; Ma, Lian Liang; Maccarrone, Giovanni; Macchiolo, Anna; Maček, Boštjan; Machado Miguens, Joana; Mackeprang, Rasmus; Madaras, Ronald; Mader, Wolfgang; Maenner, Reinhard; Maeno, Tadashi; Mättig, Peter; Mättig, Stefan; Magnoni, Luca; Magradze, Erekle; Mahboubi, Kambiz; Mahmoud, Sara; Mahout, Gilles; Maiani, Camilla; Maidantchik, Carmen; Maio, Amélia; Majewski, Stephanie; Makida, Yasuhiro; Makovec, Nikola; Mal, Prolay; Malaescu, Bogdan; Malecki, Pawel; Malecki, Piotr; Maleev, Victor; Malek, Fairouz; Mallik, Usha; Malon, David; Malone, Caitlin; Maltezos, Stavros; Malyshev, Vladimir; Malyukov, Sergei; Mameghani, Raphael; Mamuzic, Judita; Manabe, Atsushi; Mandelli, Luciano; Mandić, Igor; Mandrysch, Rocco; Maneira, José; Mangeard, Pierre-Simon; Manhaes de Andrade Filho, Luciano; Mann, Alexander; Manning, Peter; Manousakis-Katsikakis, Arkadios; Mansoulie, Bruno; Mapelli, Alessandro; Mapelli, Livio; March, Luis; Marchand, Jean-Francois; Marchese, Fabrizio; Marchiori, Giovanni; Marcisovsky, Michal; Marino, Christopher; Marroquim, Fernando; Marshall, Zach; Martens, Kalen; Marti, Lukas Fritz; Marti-Garcia, Salvador; Martin, Brian; Martin, Brian Thomas; Martin, Jean-Pierre; Martin, Tim; Martin, Victoria Jane; Martin dit Latour, Bertrand; Martin-Haugh, Stewart; Martinez, Mario; Martinez Outschoorn, Verena; Martyniuk, Alex; Marx, Marilyn; Marzano, Francesco; Marzin, Antoine; Masetti, Lucia; Mashimo, Tetsuro; Mashinistov, Ruslan; Masik, Jiri; Maslennikov, Alexey; Massa, Ignazio; Massaro, Graziano; Massol, Nicolas; Mastroberardino, Anna; Masubuchi, Tatsuya; Matricon, Pierre; Matsunaga, Hiroyuki; Matsushita, Takashi; Mattravers, Carly; Maurer, Julien; Maxfield, Stephen; Mayne, Anna; Mazini, Rachid; Mazur, Michael; Mazzaferro, Luca; Mazzanti, Marcello; Mc Kee, Shawn Patrick; McCarn, Allison; McCarthy, Robert; McCarthy, Tom; McCubbin, Norman; McFarlane, Kenneth; Mcfayden, Josh; McGlone, Helen; Mchedlidze, Gvantsa; Mclaughlan, Tom; McMahon, Steve; McPherson, Robert; Meade, Andrew; Mechnich, Joerg; Mechtel, Markus; Medinnis, Mike; Meera-Lebbai, Razzak; Meguro, Tatsuma; Mehdiyev, Rashid; Mehlhase, Sascha; Mehta, Andrew; Meier, Karlheinz; Meirose, Bernhard; Melachrinos, Constantinos; Mellado Garcia, Bruce Rafael; Meloni, Federico; Mendoza Navas, Luis; Meng, Zhaoxia; Mengarelli, Alberto; Menke, Sven; Meoni, Evelin; Mercurio, Kevin Michael; Mermod, Philippe; Merola, Leonardo; Meroni, Chiara; Merritt, Frank; Merritt, Hayes; Messina, Andrea; Metcalfe, Jessica; Mete, Alaettin Serhan; Meyer, Carsten; Meyer, Christopher; Meyer, Jean-Pierre; Meyer, Jochen; Meyer, Joerg; Meyer, Thomas Christian; Meyer, W Thomas; Miao, Jiayuan; Michal, Sebastien; Micu, Liliana; Middleton, Robin; Migas, Sylwia; Mijović, Liza; Mikenberg, Giora; Mikestikova, Marcela; Mikuž, Marko; Miller, David; Miller, Robert; Mills, Bill; Mills, Corrinne; Milov, Alexander; Milstead, David; Milstein, Dmitry; Minaenko, Andrey; Miñano Moya, Mercedes; Minashvili, Irakli; Mincer, Allen; Mindur, Bartosz; Mineev, Mikhail; Ming, Yao; Mir, Lluisa-Maria; Mirabelli, Giovanni; Mitrevski, Jovan; Mitsou, Vasiliki A; Mitsui, Shingo; Miyagawa, Paul; Mjörnmark, Jan-Ulf; Moa, Torbjoern; Moeller, Victoria; Mönig, Klaus; Möser, Nicolas; Mohapatra, Soumya; Mohr, Wolfgang; Moles-Valls, Regina; Monk, James; Monnier, Emmanuel; Montejo Berlingen, Javier; Montesano, Simone; Monticelli, Fernando; Monzani, Simone; Moore, Roger; Moorhead, Gareth; Mora Herrera, Clemencia; Moraes, Arthur; Morange, Nicolas; Morel, Julien; Morello, Gianfranco; Moreno, Deywis; Moreno Llácer, María; Morettini, Paolo; Morgenstern, Marcus; Morii, Masahiro; Morley, Anthony Keith; Mornacchi, Giuseppe; Morris, John; Morvaj, Ljiljana; Moser, Hans-Guenther; Mosidze, Maia; Moss, Josh; Mount, Richard; Mountricha, Eleni; Mouraviev, Sergei; Moyse, Edward; Mueller, Felix; Mueller, James; Mueller, Klemens; Müller, Thomas; Mueller, Timo; Muenstermann, Daniel; Munwes, Yonathan; Murray, Bill; Mussche, Ido; Musto, Elisa; Myagkov, Alexey; Myska, Miroslav; Nadal, Jordi; Nagai, Koichi; Nagano, Kunihiro; Nagarkar, Advait; Nagasaka, Yasushi; Nagel, Martin; Nairz, Armin Michael; Nakahama, Yu; Nakamura, Koji; Nakamura, Tomoaki; Nakano, Itsuo; Nanava, Gizo; Napier, Austin; Narayan, Rohin; Nash, Michael; Nattermann, Till; Naumann, Thomas; Navarro, Gabriela; Neal, Homer; Nechaeva, Polina; Neep, Thomas James; Negri, Andrea; Negri, Guido; Nektarijevic, Snezana; Nelson, Andrew; Nelson, Timothy Knight; Nemecek, Stanislav; Nemethy, Peter; Nepomuceno, Andre Asevedo; Nessi, Marzio; Neubauer, Mark; Neusiedl, Andrea; Neves, Ricardo; Nevski, Pavel; Newman, Paul; Nguyen Thi Hong, Van; Nickerson, Richard; Nicolaidou, Rosy; Nicquevert, Bertrand; Niedercorn, Francois; Nielsen, Jason; Nikiforou, Nikiforos; Nikiforov, Andriy; Nikolaenko, Vladimir; Nikolic-Audit, Irena; Nikolics, Katalin; Nikolopoulos, Konstantinos; Nilsen, Henrik; Nilsson, Paul; Ninomiya, Yoichi; Nisati, Aleandro; Nisius, Richard; Nobe, Takuya; Nodulman, Lawrence; Nomachi, Masaharu; Nomidis, Ioannis; Nordberg, Markus; Norton, Peter; Novakova, Jana; Nozaki, Mitsuaki; Nozka, Libor; Nugent, Ian Michael; Nuncio-Quiroz, Adriana-Elizabeth; Nunes Hanninger, Guilherme; Nunnemann, Thomas; Nurse, Emily; O'Brien, Brendan Joseph; O'Neale, Steve; O'Neil, Dugan; O'Shea, Val; Oakes, Louise Beth; Oakham, Gerald; Oberlack, Horst; Ocariz, Jose; Ochi, Atsuhiko; Oda, Susumu; Odaka, Shigeru; Odier, Jerome; Ogren, Harold; Oh, Alexander; Oh, Seog; Ohm, Christian; Ohshima, Takayoshi; Okawa, Hideki; Okumura, Yasuyuki; Okuyama, Toyonobu; Olariu, Albert; Olchevski, Alexander; Olivares Pino, Sebastian Andres; Oliveira, Miguel Alfonso; Oliveira Damazio, Denis; Oliver Garcia, Elena; Olivito, Dominick; Olszewski, Andrzej; Olszowska, Jolanta; Onofre, António; Onyisi, Peter; Oram, Christopher; Oreglia, Mark; Oren, Yona; Orestano, Domizia; Orlando, Nicola; Orlov, Iliya; Oropeza Barrera, Cristina; Orr, Robert; Osculati, Bianca; Ospanov, Rustem; Osuna, Carlos; Otero y Garzon, Gustavo; Ottersbach, John; Ouchrif, Mohamed; Ouellette, Eric; Ould-Saada, Farid; Ouraou, Ahmimed; Ouyang, Qun; Ovcharova, Ana; Owen, Mark; Owen, Simon; Ozcan, Veysi Erkcan; Ozturk, Nurcan; Pacheco Pages, Andres; Padilla Aranda, Cristobal; Pagan Griso, Simone; Paganis, Efstathios; Paige, Frank; Pais, Preema; Pajchel, Katarina; Palacino, Gabriel; Paleari, Chiara; Palestini, Sandro; Pallin, Dominique; Palma, Alberto; Palmer, Jody; Pan, Yibin; Panagiotopoulou, Evgenia; Pani, Priscilla; Panikashvili, Natalia; Panitkin, Sergey; Pantea, Dan; Papadelis, Aras; Papadopoulou, Theodora; Paramonov, Alexander; Paredes Hernandez, Daniela; Park, Woochun; Parker, Andy; Parodi, Fabrizio; Parsons, John; Parzefall, Ulrich; Pashapour, Shabnaz; Pasqualucci, Enrico; Passaggio, Stefano; Passeri, Antonio; Pastore, Fernanda; Pastore, Francesca; Pásztor, Gabriella; Pataraia, Sophio; Patel, Nikhul; Pater, Joleen; Patricelli, Sergio; Pauly, Thilo; Pecsy, Martin; Pedraza Morales, Maria Isabel; Peleganchuk, Sergey; Pelikan, Daniel; Peng, Haiping; Penning, Bjoern; Penson, Alexander; Penwell, John; Perantoni, Marcelo; Perez, Kerstin; Perez Cavalcanti, Tiago; Perez Codina, Estel; Pérez García-Estañ, María Teresa; Perez Reale, Valeria; Perini, Laura; Pernegger, Heinz; Perrino, Roberto; Perrodo, Pascal; Peshekhonov, Vladimir; Peters, Krisztian; Petersen, Brian; Petersen, Jorgen; Petersen, Troels; Petit, Elisabeth; Petridis, Andreas; Petridou, Chariclia; Petrolo, Emilio; Petrucci, Fabrizio; Petschull, Dennis; Petteni, Michele; Pezoa, Raquel; Phan, Anna; Phillips, Peter William; Piacquadio, Giacinto; Picazio, Attilio; Piccaro, Elisa; Piccinini, Maurizio; Piec, Sebastian Marcin; Piegaia, Ricardo; Pignotti, David; Pilcher, James; Pilkington, Andrew; Pina, João Antonio; Pinamonti, Michele; Pinder, Alex; Pinfold, James; Pinto, Belmiro; Pizio, Caterina; Plamondon, Mathieu; Pleier, Marc-Andre; Plotnikova, Elena; Poblaguev, Andrei; Poddar, Sahill; Podlyski, Fabrice; Poggioli, Luc; Poghosyan, Tatevik; Pohl, Martin; Polesello, Giacomo; Policicchio, Antonio; Polini, Alessandro; Poll, James; Polychronakos, Venetios; Pomeroy, Daniel; Pommès, Kathy; Pontecorvo, Ludovico; Pope, Bernard; Popeneciu, Gabriel Alexandru; Popovic, Dragan; Poppleton, Alan; Portell Bueso, Xavier; Pospelov, Guennady; Pospisil, Stanislav; Potrap, Igor; Potter, Christina; Potter, Christopher; Poulard, Gilbert; Poveda, Joaquin; Pozdnyakov, Valery; Prabhu, Robindra; Pralavorio, Pascal; Pranko, Aliaksandr; Prasad, Srivas; Pravahan, Rishiraj; Prell, Soeren; Pretzl, Klaus Peter; Price, Darren; Price, Joe; Price, Lawrence; Prieur, Damien; Primavera, Margherita; Prokofiev, Kirill; Prokoshin, Fedor; Protopopescu, Serban; Proudfoot, James; Prudent, Xavier; Przybycien, Mariusz; Przysiezniak, Helenka; Psoroulas, Serena; Ptacek, Elizabeth; Pueschel, Elisa; Purdham, John; Purohit, Milind; Puzo, Patrick; Pylypchenko, Yuriy; Qian, Jianming; Quadt, Arnulf; Quarrie, David; Quayle, William; Quinonez, Fernando; Raas, Marcel; Radescu, Voica; Radloff, Peter; Rador, Tonguc; Ragusa, Francesco; Rahal, Ghita; Rahimi, Amir; Rahm, David; Rajagopalan, Srinivasan; Rammensee, Michael; Rammes, Marcus; Randle-Conde, Aidan Sean; Randrianarivony, Koloina; Rauscher, Felix; Rave, Tobias Christian; Raymond, Michel; Read, Alexander Lincoln; Rebuzzi, Daniela; Redelbach, Andreas; Redlinger, George; Reece, Ryan; Reeves, Kendall; Reinherz-Aronis, Erez; Reinsch, Andreas; Reisinger, Ingo; Rembser, Christoph; Ren, Zhongliang; Renaud, Adrien; Rescigno, Marco; Resconi, Silvia; Resende, Bernardo; Reznicek, Pavel; Rezvani, Reyhaneh; Richter, Robert; Richter-Was, Elzbieta; Ridel, Melissa; Rijpstra, Manouk; Rijssenbeek, Michael; Rimoldi, Adele; Rinaldi, Lorenzo; Rios, Ryan Randy; Riu, Imma; Rivoltella, Giancesare; Rizatdinova, Flera; Rizvi, Eram; Robertson, Steven; Robichaud-Veronneau, Andree; Robinson, Dave; Robinson, James; Robson, Aidan; Rocha de Lima, Jose Guilherme; Roda, Chiara; Roda Dos Santos, Denis; Roe, Adam; Roe, Shaun; Røhne, Ole; Rolli, Simona; Romaniouk, Anatoli; Romano, Marino; Romeo, Gaston; Romero Adam, Elena; Roos, Lydia; Ros, Eduardo; Rosati, Stefano; Rosbach, Kilian; Rose, Anthony; Rose, Matthew; Rosenbaum, Gabriel; Rosenberg, Eli; Rosendahl, Peter Lundgaard; Rosenthal, Oliver; Rosselet, Laurent; Rossetti, Valerio; Rossi, Elvira; Rossi, Leonardo Paolo; Rotaru, Marina; Roth, Itamar; Rothberg, Joseph; Rousseau, David; Royon, Christophe; Rozanov, Alexander; Rozen, Yoram; Ruan, Xifeng; Rubbo, Francesco; Rubinskiy, Igor; Ruckert, Benjamin; Ruckstuhl, Nicole; Rud, Viacheslav; Rudolph, Christian; Rudolph, Gerald; Rühr, Frederik; Ruiz-Martinez, Aranzazu; Rumyantsev, Leonid; Rurikova, Zuzana; Rusakovich, Nikolai; Rutherfoord, John; Ruwiedel, Christoph; Ruzicka, Pavel; Ryabov, Yury; Ryan, Patrick; Rybar, Martin; Rybkin, Grigori; Ryder, Nick; Saavedra, Aldo; Sadeh, Iftach; Sadrozinski, Hartmut; Sadykov, Renat; Safai Tehrani, Francesco; Sakamoto, Hiroshi; Salamanna, Giuseppe; Salamon, Andrea; Saleem, Muhammad; Salek, David; Salihagic, Denis; Salnikov, Andrei; Salt, José; Salvachua Ferrando, Belén; Salvatore, Daniela; Salvatore, Pasquale Fabrizio; Salvucci, Antonio; Salzburger, Andreas; Sampsonidis, Dimitrios; Samset, Björn Hallvard; Sanchez, Arturo; Sanchez Martinez, Victoria; Sandaker, Heidi; Sander, Heinz Georg; Sanders, Michiel; Sandhoff, Marisa; Sandoval, Tanya; Sandoval, Carlos; Sandstroem, Rikard; Sankey, Dave; Sansoni, Andrea; Santamarina Rios, Cibran; Santoni, Claudio; Santonico, Rinaldo; Santos, Helena; Saraiva, João; Sarangi, Tapas; Sarkisyan-Grinbaum, Edward; Sarri, Francesca; Sartisohn, Georg; Sasaki, Osamu; Sasao, Noboru; Satsounkevitch, Igor; Sauvage, Gilles; Sauvan, Emmanuel; Sauvan, Jean-Baptiste; Savard, Pierre; Savinov, Vladimir; Savu, Dan Octavian; Sawyer, Lee; Saxon, David; Saxon, James; Sbarra, Carla; Sbrizzi, Antonio; Scallon, Olivia; Scannicchio, Diana; Scarcella, Mark; Schaarschmidt, Jana; Schacht, Peter; Schaefer, Douglas; Schäfer, Uli; Schaepe, Steffen; Schaetzel, Sebastian; Schaffer, Arthur; Schaile, Dorothee; Schamberger, R. Dean; Schamov, Andrey; Scharf, Veit; Schegelsky, Valery; Scheirich, Daniel; Schernau, Michael; Scherzer, Max; Schiavi, Carlo; Schieck, Jochen; Schioppa, Marco; Schlenker, Stefan; Schmidt, Evelyn; Schmieden, Kristof; Schmitt, Christian; Schmitt, Sebastian; Schmitz, Martin; Schneider, Basil; Schnoor, Ulrike; Schöning, André; Schorlemmer, Andre Lukas; Schott, Matthias; Schouten, Doug; Schovancova, Jaroslava; Schram, Malachi; Schroeder, Christian; Schroer, Nicolai; Schultens, Martin Johannes; Schultes, Joachim; Schultz-Coulon, Hans-Christian; Schulz, Holger; Schumacher, Markus; Schumm, Bruce; Schune, Philippe; Schwanenberger, Christian; Schwartzman, Ariel; Schwemling, Philippe; Schwienhorst, Reinhard; Schwierz, Rainer; Schwindling, Jerome; Schwindt, Thomas; Schwoerer, Maud; Sciolla, Gabriella; Scott, Bill; Searcy, Jacob; Sedov, George; Sedykh, Evgeny; Seidel, Sally; Seiden, Abraham; Seifert, Frank; Seixas, José; Sekhniaidze, Givi; Sekula, Stephen; Selbach, Karoline Elfriede; Seliverstov, Dmitry; Sellden, Bjoern; Sellers, Graham; Seman, Michal; Semprini-Cesari, Nicola; Serfon, Cedric; Serin, Laurent; Serkin, Leonid; Seuster, Rolf; Severini, Horst; Sfyrla, Anna; Shabalina, Elizaveta; Shamim, Mansoora; Shan, Lianyou; Shank, James; Shao, Qi Tao; Shapiro, Marjorie; Shatalov, Pavel; Shaw, Kate; Sherman, Daniel; Sherwood, Peter; Shibata, Akira; Shimizu, Shima; Shimojima, Makoto; Shin, Taeksu; Shiyakova, Maria; Shmeleva, Alevtina; Shochet, Mel; Short, Daniel; Shrestha, Suyog; Shulga, Evgeny; Shupe, Michael; Sicho, Petr; Sidoti, Antonio; Siegert, Frank; Sijacki, Djordje; Silbert, Ohad; Silva, José; Silver, Yiftah; Silverstein, Daniel; Silverstein, Samuel; Simak, Vladislav; Simard, Olivier; Simic, Ljiljana; Simion, Stefan; Simioni, Eduard; Simmons, Brinick; Simoniello, Rosa; Simonyan, Margar; Sinervo, Pekka; Sinev, Nikolai; Sipica, Valentin; Siragusa, Giovanni; Sircar, Anirvan; Sisakyan, Alexei; Sivoklokov, Serguei; Sjölin, Jörgen; Sjursen, Therese; Skinnari, Louise Anastasia; Skottowe, Hugh Philip; Skovpen, Kirill; Skubic, Patrick; Slater, Mark; Slavicek, Tomas; Sliwa, Krzysztof; Smakhtin, Vladimir; Smart, Ben; Smirnov, Sergei; Smirnov, Yury; Smirnova, Lidia; Smirnova, Oxana; Smith, Ben Campbell; Smith, Douglas; Smith, Kenway; Smizanska, Maria; Smolek, Karel; Snesarev, Andrei; Snow, Steve; Snow, Joel; Snyder, Scott; Sobie, Randall; Sodomka, Jaromir; Soffer, Abner; Solans, Carlos; Solar, Michael; Solc, Jaroslav; Soldatov, Evgeny; Soldevila, Urmila; Solfaroli Camillocci, Elena; Solodkov, Alexander; Solovyanov, Oleg; Soni, Nitesh; Sopko, Vit; Sopko, Bruno; Sosebee, Mark; Soualah, Rachik; Soukharev, Andrey; Spagnolo, Stefania; Spanò, Francesco; Spighi, Roberto; Spigo, Giancarlo; Spila, Federico; Spiwoks, Ralf; Spousta, Martin; Spreitzer, Teresa; Spurlock, Barry; St Denis, Richard Dante; Stahlman, Jonathan; Stamen, Rainer; Stanecka, Ewa; Stanek, Robert; Stanescu, Cristian; Stanescu-Bellu, Madalina; Stapnes, Steinar; Starchenko, Evgeny; Stark, Jan; Staroba, Pavel; Starovoitov, Pavel; Staszewski, Rafal; Staude, Arnold; Stavina, Pavel; Steele, Genevieve; Steinbach, Peter; Steinberg, Peter; Stekl, Ivan; Stelzer, Bernd; Stelzer, Harald Joerg; Stelzer-Chilton, Oliver; Stenzel, Hasko; Stern, Sebastian; Stewart, Graeme; Stillings, Jan Andre; Stockton, Mark; Stoerig, Kathrin; Stoicea, Gabriel; Stonjek, Stefan; Strachota, Pavel; Stradling, Alden; Straessner, Arno; Strandberg, Jonas; Strandberg, Sara; Strandlie, Are; Strang, Michael; Strauss, Emanuel; Strauss, Michael; Strizenec, Pavol; Ströhmer, Raimund; Strom, David; Strong, John; Stroynowski, Ryszard; Strube, Jan; Stugu, Bjarne; Stumer, Iuliu; Stupak, John; Sturm, Philipp; Styles, Nicholas Adam; Soh, Dart-yin; Su, Dong; Subramania, Halasya Siva; Succurro, Antonella; Sugaya, Yorihito; Suhr, Chad; Suk, Michal; Sulin, Vladimir; Sultansoy, Saleh; Sumida, Toshi; Sun, Xiaohu; Sundermann, Jan Erik; Suruliz, Kerim; Susinno, Giancarlo; Sutton, Mark; Suzuki, Yu; Suzuki, Yuta; Svatos, Michal; Swedish, Stephen; Sykora, Ivan; Sykora, Tomas; Sánchez, Javier; Ta, Duc; Tackmann, Kerstin; Taffard, Anyes; Tafirout, Reda; Taiblum, Nimrod; Takahashi, Yuta; Takai, Helio; Takashima, Ryuichi; Takeda, Hiroshi; Takeshita, Tohru; Takubo, Yosuke; Talby, Mossadek; Talyshev, Alexey; Tamsett, Matthew; Tanaka, Junichi; Tanaka, Reisaburo; Tanaka, Satoshi; Tanaka, Shuji; Tanasijczuk, Andres Jorge; Tani, Kazutoshi; Tannoury, Nancy; Tapprogge, Stefan; Tardif, Dominique; Tarem, Shlomit; Tarrade, Fabien; Tartarelli, Giuseppe Francesco; Tas, Petr; Tasevsky, Marek; Tassi, Enrico; Tatarkhanov, Mous; Tayalati, Yahya; Taylor, Christopher; Taylor, Frank; Taylor, Geoffrey; Taylor, Wendy; Teinturier, Marthe; Teixeira Dias Castanheira, Matilde; Teixeira-Dias, Pedro; Temming, Kim Katrin; Ten Kate, Herman; Teng, Ping-Kun; Terada, Susumu; Terashi, Koji; Terron, Juan; Testa, Marianna; Teuscher, Richard; Therhaag, Jan; Theveneaux-Pelzer, Timothée; Thoma, Sascha; Thomas, Juergen; Thompson, Emily; Thompson, Paul; Thompson, Peter; Thompson, Stan; Thomsen, Lotte Ansgaard; Thomson, Evelyn; Thomson, Mark; Thun, Rudolf; Tian, Feng; Tibbetts, Mark James; Tic, Tomáš; Tikhomirov, Vladimir; Tikhonov, Yury; Timoshenko, Sergey; Tipton, Paul; Tique Aires Viegas, Florbela De Jes; Tisserant, Sylvain; Todorov, Theodore; Todorova-Nova, Sharka; Toggerson, Brokk; Tojo, Junji; Tokár, Stanislav; Tokushuku, Katsuo; Tollefson, Kirsten; Tomoto, Makoto; Tompkins, Lauren; Toms, Konstantin; Tonoyan, Arshak; Topfel, Cyril; Topilin, Nikolai; Torchiani, Ingo; Torrence, Eric; Torres, Heberth; Torró Pastor, Emma; Toth, Jozsef; Touchard, Francois; Tovey, Daniel; Trefzger, Thomas; Tremblet, Louis; Tricoli, Alesandro; Trigger, Isabel Marian; Trincaz-Duvoid, Sophie; Tripiana, Martin; Trischuk, William; Trocmé, Benjamin; Troncon, Clara; Trottier-McDonald, Michel; Trzebinski, Maciej; Trzupek, Adam; Tsarouchas, Charilaos; Tseng, Jeffrey; Tsiakiris, Menelaos; Tsiareshka, Pavel; Tsionou, Dimitra; Tsipolitis, Georgios; Tsiskaridze, Shota; Tsiskaridze, Vakhtang; Tskhadadze, Edisher; Tsukerman, Ilya; Tsulaia, Vakhtang; Tsung, Jieh-Wen; Tsuno, Soshi; Tsybychev, Dmitri; Tua, Alan; Tudorache, Alexandra; Tudorache, Valentina; Tuggle, Joseph; Turala, Michal; Turecek, Daniel; Turk Cakir, Ilkay; Turlay, Emmanuel; Turra, Ruggero; Tuts, Michael; Tykhonov, Andrii; Tylmad, Maja; Tyndel, Mike; Tzanakos, George; Uchida, Kirika; Ueda, Ikuo; Ueno, Ryuichi; Ugland, Maren; Uhlenbrock, Mathias; Uhrmacher, Michael; Ukegawa, Fumihiko; Unal, Guillaume; Undrus, Alexander; Unel, Gokhan; Unno, Yoshinobu; Urbaniec, Dustin; Usai, Giulio; Uslenghi, Massimiliano; Vacavant, Laurent; Vacek, Vaclav; Vachon, Brigitte; Vahsen, Sven; Valenta, Jan; Valente, Paolo; Valentinetti, Sara; Valero, Alberto; Valkar, Stefan; Valladolid Gallego, Eva; Vallecorsa, Sofia; Valls Ferrer, Juan Antonio; van der Graaf, Harry; van der Kraaij, Erik; Van Der Leeuw, Robin; van der Poel, Egge; van der Ster, Daniel; van Eldik, Niels; van Gemmeren, Peter; van Vulpen, Ivo; Vanadia, Marco; Vandelli, Wainer; Vaniachine, Alexandre; Vankov, Peter; Vannucci, Francois; Vari, Riccardo; Varol, Tulin; Varouchas, Dimitris; Vartapetian, Armen; Varvell, Kevin; Vassilakopoulos, Vassilios; Vazeille, Francois; Vazquez Schroeder, Tamara; Vegni, Guido; Veillet, Jean-Jacques; Veloso, Filipe; Veness, Raymond; Veneziano, Stefano; Ventura, Andrea; Ventura, Daniel; Venturi, Manuela; Venturi, Nicola; Vercesi, Valerio; Verducci, Monica; Verkerke, Wouter; Vermeulen, Jos; Vest, Anja; Vetterli, Michel; Vichou, Irene; Vickey, Trevor; Vickey Boeriu, Oana Elena; Viehhauser, Georg; Viel, Simon; Villa, Mauro; Villaplana Perez, Miguel; Vilucchi, Elisabetta; Vincter, Manuella; Vinek, Elisabeth; Vinogradov, Vladimir; Virchaux, Marc; Virzi, Joseph; Vitells, Ofer; Viti, Michele; Vivarelli, Iacopo; Vives Vaque, Francesc; Vlachos, Sotirios; Vladoiu, Dan; Vlasak, Michal; Vogel, Adrian; Vokac, Petr; Volpi, Guido; Volpi, Matteo; Volpini, Giovanni; von der Schmitt, Hans; von Loeben, Joerg; von Radziewski, Holger; von Toerne, Eckhard; Vorobel, Vit; Vorwerk, Volker; Vos, Marcel; Voss, Rudiger; Voss, Thorsten Tobias; Vossebeld, Joost; Vranjes, Nenad; Vranjes Milosavljevic, Marija; Vrba, Vaclav; Vreeswijk, Marcel; Vu Anh, Tuan; Vuillermet, Raphael; Vukotic, Ilija; Wagner, Wolfgang; Wagner, Peter; Wahlen, Helmut; Wahrmund, Sebastian; Wakabayashi, Jun; Walch, Shannon; Walder, James; Walker, Rodney; Walkowiak, Wolfgang; Wall, Richard; Waller, Peter; Wang, Chiho; Wang, Haichen; Wang, Hulin; Wang, Jike; Wang, Jin; Wang, Rui; Wang, Song-Ming; Wang, Tan; Warburton, Andreas; Ward, Patricia; Warsinsky, Markus; Washbrook, Andrew; Wasicki, Christoph; Watkins, Peter; Watson, Alan; Watson, Ian; Watson, Miriam; Watts, Gordon; Watts, Stephen; Waugh, Anthony; Waugh, Ben; Weber, Marc; Weber, Michele; Weber, Pavel; Weidberg, Anthony; Weigell, Philipp; Weingarten, Jens; Weiser, Christian; Wellenstein, Hermann; Wells, Phillippa; Wenaus, Torre; Wendland, Dennis; Weng, Zhili; Wengler, Thorsten; Wenig, Siegfried; Wermes, Norbert; Werner, Matthias; Werner, Per; Werth, Michael; Wessels, Martin; Wetter, Jeffrey; Weydert, Carole; Whalen, Kathleen; Wheeler-Ellis, Sarah Jane; White, Andrew; White, Martin; White, Sebastian; Whitehead, Samuel Robert; Whiteson, Daniel; Whittington, Denver; Wicek, Francois; Wicke, Daniel; Wickens, Fred; Wiedenmann, Werner; Wielers, Monika; Wienemann, Peter; Wiglesworth, Craig; Wiik-Fuchs, Liv Antje Mari; Wijeratne, Peter Alexander; Wildauer, Andreas; Wildt, Martin Andre; Wilhelm, Ivan; Wilkens, Henric George; Will, Jonas Zacharias; Williams, Eric; Williams, Hugh; Willis, William; Willocq, Stephane; Wilson, John; Wilson, Michael Galante; Wilson, Alan; Wingerter-Seez, Isabelle; Winkelmann, Stefan; Winklmeier, Frank; Wittgen, Matthias; Wollstadt, Simon Jakob; Wolter, Marcin Wladyslaw; Wolters, Helmut; Wong, Wei-Cheng; Wooden, Gemma; Wosiek, Barbara; Wotschack, Jorg; Woudstra, Martin; Wozniak, Krzysztof; Wraight, Kenneth; Wright, Catherine; Wright, Michael; Wrona, Bozydar; Wu, Sau Lan; Wu, Xin; Wu, Yusheng; Wulf, Evan; Wynne, Benjamin; Xella, Stefania; Xiao, Meng; Xie, Song; Xu, Chao; Xu, Da; Yabsley, Bruce; Yacoob, Sahal; Yamada, Miho; Yamaguchi, Hiroshi; Yamamoto, Akira; Yamamoto, Kyoko; Yamamoto, Shimpei; Yamamura, Taiki; Yamanaka, Takashi; Yamaoka, Jared; Yamazaki, Takayuki; Yamazaki, Yuji; Yan, Zhen; Yang, Haijun; Yang, Un-Ki; Yang, Yi; Yang, Zhaoyu; Yanush, Serguei; Yao, Liwen; Yao, Yushu; Yasu, Yoshiji; Ybeles Smit, Gabriel Valentijn; Ye, Jingbo; Ye, Shuwei; Yilmaz, Metin; Yoosoofmiya, Reza; Yorita, Kohei; Yoshida, Riktura; Young, Charles; Young, Christopher John; Youssef, Saul; Yu, Dantong; Yu, Jaehoon; Yu, Jie; Yuan, Li; Yurkewicz, Adam; Zabinski, Bartlomiej; Zaidan, Remi; Zaitsev, Alexander; Zajacova, Zuzana; Zanello, Lucia; Zaytsev, Alexander; Zeitnitz, Christian; Zeman, Martin; Zemla, Andrzej; Zendler, Carolin; Zenin, Oleg; Ženiš, Tibor; Zinonos, Zinonas; Zenz, Seth; Zerwas, Dirk; Zevi della Porta, Giovanni; Zhan, Zhichao; Zhang, Dongliang; Zhang, Huaqiao; Zhang, Jinlong; Zhang, Xueyao; Zhang, Zhiqing; Zhao, Long; Zhao, Tianchi; Zhao, Zhengguo; Zhemchugov, Alexey; Zhong, Jiahang; Zhou, Bing; Zhou, Ning; Zhou, Yue; Zhu, Cheng Guang; Zhu, Hongbo; Zhu, Junjie; Zhu, Yingchun; Zhuang, Xuai; Zhuravlov, Vadym; Zieminska, Daria; Zimin, Nikolai; Zimmermann, Robert; Zimmermann, Simone; Zimmermann, Stephanie; Ziolkowski, Michael; Zitoun, Robert; Živković, Lidija; Zmouchko, Viatcheslav; Zobernig, Georg; Zoccoli, Antonio; zur Nedden, Martin; Zutshi, Vishnu; Zwalinski, Lukasz

    2013-02-26

    Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at $\\sqrt{s_{NN}}$ = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |$\\eta$| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-$k_t$ algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," $R_{cp}$. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. $R_{cp}$ varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius ...

  12. Effect of low-molecular-weight beta-cyclodextrin polymer on release of drugs from mucoadhesive buccal film dosage forms.

    Science.gov (United States)

    Arakawa, Yotaro; Kawakami, Shigeru; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2005-09-01

    We investigated the effect of low-molecular-weight beta-cyclodextrin (beta-CyD) polymer on in vitro release of two drugs with different lipophilicities (i.e., lidocaine and ketoprofen) from mucoadhesive buccal film dosage forms. When beta-CyD polymer was added to hydroxypropylcellulose (HPC) or polyvinylalcohol (PVA) film dosage forms, the release of lidocaine into artificial saliva (pH 5.7) was reduced by 40% of the control. In contrast, the release of ketoprofen from the polymer film was enhanced by addition of beta-CyD polymer to the vehicle. When lidocaine and ketoprofen was incubated with beta-CyD polymer in the artificial saliva, concentration of free lidocaine molecules decreased in a beta-CyD polymer concentration-dependent manner. The association constant with beta-CyD polymer was 6.9+/-0.6 and 520+/-90 M(-1) for lidocaine and ketoprofen, respectively. Retarded release of the hydrophilic lidocaine by beta-CyD polymer might be due to the decrease in thermodynamic activity by inclusion complex formation, whereas enhanced release of the lipophilic ketoprofen by the beta-CyD polymer might be due to prevention of recrystallization occurring after contacting the film with aqueous solution. Thus, effects of low-molecular-weight beta-CyD polymer to the drug release rate from film dosage forms would vary according to the strength of interaction with and the solubility of active ingredient.

  13. Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

    Science.gov (United States)

    Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-12-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

    Science.gov (United States)

    Shen, Jie; Burgess, Diane J

    2012-07-01

    This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  15. Accelerated in vitro release testing methods for extended release parenteral dosage forms

    Science.gov (United States)

    Shen, Jie; Burgess, Diane J.

    2012-01-01

    Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

  16. Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation.

    Science.gov (United States)

    Allavena, Giulia; Cuomo, Francesca; Baumgartner, Georg; Bele, Tadeja; Sellgren, Alexander Yarar; Oo, Kyaw Soe; Johnson, Kaylee; Gogvadze, Vladimir; Zhivotovsky, Boris; Kaminskyy, Vitaliy O

    2018-01-01

    Macroautophagy/autophagy inhibition under stress conditions is often associated with increased cell death. We found that under nutrient limitation, activation of CASP8/caspase-8 was significantly increased in autophagy-deficient lung cancer cells, which precedes mitochondria outer membrane permeabilization (MOMP), CYCS/cytochrome c release, and activation of CASP9/caspase-9, indicating that under such conditions the activation of CASP8 is a primary event in the initiation of apoptosis as well as essential to reduce clonogenic survival of autophagy-deficient cells. Starvation leads to suppression of CFLAR proteosynthesis and accumulation of CASP8 in SQSTM1 puncta. Overexpression of CFLARs reduces CASP8 activation and apoptosis during starvation, while its silencing promotes efficient activation of CASP8 and apoptosis in autophagy-deficient U1810 lung cancer cells even under nutrient-rich conditions. Similar to starvation, inhibition of protein translation leads to efficient activation of CASP8 and cell death in autophagy-deficient lung cancer cells. Thus, here for the first time we report that suppressed translation leads to activation of CASP8-dependent apoptosis in autophagy-deficient NSCLC cells under conditions of nutrient limitation. Our data suggest that targeting translational machinery can be beneficial for elimination of autophagy-deficient cells via the CASP8-dependent apoptotic pathway.

  17. Suppression factors in diffractive photoproduction of dijets

    International Nuclear Information System (INIS)

    Klasen, Michael; Kramer, Gustav

    2010-06-01

    After new publications of H1 data for the diffractive photoproduction of dijets, which overlap with the earlier published H1 data and the recently published data of the ZEUS collaboration, have appeared, we have recalculated the cross sections for this process in next-to-leading order (NLO) of perturbative QCD to see whether they can be interpreted consistently. The results of these calculations are compared to the data of both collaborations. We find that the NLO cross sections disagree with the data, showing that factorization breaking occurs at that order. If direct and resolved contributions are both suppressed by the same amount, the global suppression factor depends on the transverse-energy cut. However, by suppressing only the resolved contribution, also reasonably good agreement with all the data is found with a suppression factor independent of the transverse-energy cut. (orig.)

  18. Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

    Science.gov (United States)

    Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

    2014-02-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  19. Endotoxin dosage in sepsis

    Directory of Open Access Journals (Sweden)

    Vincenzo Rondinelli

    2012-03-01

    Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

  20. Sedation and mechanical antinociception after intravenous administration of detomidine in donkeys: a dosage-effect study.

    Science.gov (United States)

    Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Varner, Kelley M; Robinson, Lauren S

    2015-02-21

    There is limited, useful, scientific information on detomidine in donkeys. This study compared the effects of intravenous saline, detomidine (10, 13.5, 17 and 20 μg/kg) and acepromazine (50 μg/kg) in donkeys by computing areas under the curve for 0-30, 30-60 and 60-120 minutes (AUC0-30, AUC30-60 and AUC60-120) for sedation scores, head heights and mechanical nociceptive thresholds (MNTs). For sedation scores, all detomidine treatments, except 10 μg/kg, increased AUC0-30 values compared with saline, and AUC0-30 values were larger for 17 μg/kg detomidine than for acepromazine. All head height AUC values were lower for detomidine than for saline (except AUC60-120 for 10 μg/kg detomidine) and acepromazine (except AUC0-30 for 10 and 20 μg/kg detomidine, and AUC60-120 for 10 μg/kg detomidine). For MNTs, all detomidine treatments increased AUC0-30 and AUC30-60 values compared with saline and acepromazine; AUC30-60 values were smaller for 10 μg/kg than for 17 and 20 μg/kg detomidine. MNT AUC60-120 values were larger for 20 μg/kg detomidine than for saline, 10 μg/kg detomidine and acepromazine. Detomidine induced sedation and antinociception, but only antinociception was dosage dependent. Selection of detomidine dosage for donkeys may depend on the required duration of sedation and/or degree of analgesia. British Veterinary Association.

  1. Adiabatic Low-Pass J Filters for Artifact Suppression in Heteronuclear NMR

    DEFF Research Database (Denmark)

    Meier, Sebastian; Benie, Andrew J; Duus, Jens Øllgaard

    2009-01-01

    NMR artifact purging: Modern NMR experiments depend on efficient coherence transfer pathways for their sensitivity and on suppression of undesired pathways leading to artifacts for their spectral clarity. A novel robust adiabatic element suppresses hard-to-get-at artifacts....

  2. Intrathecal baclofen in multiple sclerosis and spinal cord injury: complications and long-term dosage evolution.

    Science.gov (United States)

    Draulans, Nathalie; Vermeersch, Kristof; Degraeuwe, Bart; Meurrens, Tom; Peers, Koen; Nuttin, Bart; Kiekens, Carlotte

    2013-12-01

    To investigate the long-term dosage evolution and complication rate of intrathecal baclofen use in multiple sclerosis and spinal cord injury patients, based on a large population with a long follow-up. Retrospective data analysis. Academic hospital. Patients with multiple sclerosis (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump implanted at the University Hospitals Leuven between 1988 and 2009. Medical records review of included patients in August 2010. Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after 3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed using a mixed-effect linear model. In 130 patients with a mean follow-up of 63 months, comprising 797 pump years, 104 complications were recorded. This corresponds to a complication rate of 0.011 per month, equally divided among both groups. Seventy-eight of these complications were catheter related. The mean dosage of baclofen stabilizes two years after implantation at 323 µg/day in the multiple sclerosis population. In spinal cord injury patients the daily dose only stabilizes after five years at a significantly higher dosage (504 µg/day). No significant increase in dosage is seen in the long term. In multiple sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a complication rate of 1% per month. Complications are mainly due to catheter-related problems (74%). The intrathecal baclofen dosage stabilizes in the long term, indicating that long-term tolerance, defined as progressive diminution of the susceptibility to the effects of a drug, is not present.

  3. Spectrophotometric Determination of Cilostazol in Tablet Dosage Form

    African Journals Online (AJOL)

    Purpose: To develop simple, rapid and selective spectrophotometric methods for the determination of cilostazol in tablet dosage form. Methods: Cilostazol was dissolved in 50 % methanol and its absorbance was scanned by ultraviolet (UV) spectrophotometry. Both linear regression equation and standard absorptivity were ...

  4. Fourteen days oral administration of therapeutic dosage of some ...

    African Journals Online (AJOL)

    Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

  5. Suppression of Mediator is regulated by Cdk8-dependent Grr1 turnover of the Med3 coactivator.

    Science.gov (United States)

    Gonzalez, Deyarina; Hamidi, Nurul; Del Sol, Ricardo; Benschop, Joris J; Nancy, Thomas; Li, Chao; Francis, Lewis; Tzouros, Manuel; Krijgsveld, Jeroen; Holstege, Frank C P; Conlan, R Steven

    2014-02-18

    Mediator, an evolutionary conserved large multisubunit protein complex with a central role in regulating RNA polymerase II-transcribed genes, serves as a molecular switchboard at the interface between DNA binding transcription factors and the general transcription machinery. Mediator subunits include the Cdk8 module, which has both positive and negative effects on activator-dependent transcription through the activity of the cyclin-dependent kinase Cdk8, and the tail module, which is required for positive and negative regulation of transcription, correct preinitiation complex formation in basal and activated transcription, and Mediator recruitment. Currently, the molecular mechanisms governing Mediator function remain largely undefined. Here we demonstrate an autoregulatory mechanism used by Mediator to repress transcription through the activity of distinct components of different modules. We show that the function of the tail module component Med3, which is required for transcription activation, is suppressed by the kinase activity of the Cdk8 module. Med3 interacts with, and is phosphorylated by, Cdk8; site-specific phosphorylation triggers interaction with and degradation by the Grr1 ubiquitin ligase, thereby preventing transcription activation. This active repression mechanism involving Grr1-dependent ubiquitination of Med3 offers a rationale for the substoichiometric levels of the tail module that are found in purified Mediator and the corresponding increase in tail components seen in cdk8 mutants.

  6. Optimizing the dosage of stabilizing chemical

    OpenAIRE

    Harjula, Tomi

    2013-01-01

    A chemical company provides chemical treatment at customer mill in paper industry. This thesis work was done to determine the optimum dosage of stabilizing chemical. The theoretical framework explains the basics of paper brightness and bleaching and how these topics are connected to each other. The knowledge gained is very valuable and can possibly be used in the future in other similar applications as well. This thesis work contains confidential back ground information. Key ...

  7. Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

    Science.gov (United States)

    Kaeley, Gurjit S; Evangelisto, Amy M; Nishio, Midori J; Goss, Sandra L; Liu, Shufang; Kalabic, Jasmina; Kupper, Hartmut

    2016-08-01

    To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

  8. [Post-marketing re-evaluation about usage and dosage of Chinese medicine based on human population pharmacokinetics].

    Science.gov (United States)

    Jiang, Junjie; Xie, Yanming

    2011-10-01

    The usage and dosage of Chinese patent medicine are determined by rigorous evaluation which include four clinical trail stages: I, II, III. But the usage and dosage of Chinese patent medicine are lacked re-evaluation after marketing. And this lead to unchanging or fixed of the usage and dosage of Chinese patent medicine instead of different quantity based on different situations in individual patients. The situation of Chinese patent medicine used in clinical application is far away from the idea of the "Treatment based on syndrome differentiation" in traditional Chinese medicine and personalized therapy. Human population pharmacokinetics provides data support to the personalized therapy in clinical application, and achieved the postmarking reevaluating of the usage and dosage of Chinese patent medicine. This paper briefly introduced the present situation, significance and the application of human population pharmacokinetics about re-evaluation of the usage and dosage of Chinese patent medicine after marketing.

  9. Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

    Science.gov (United States)

    Phumsatitpong, Chayarndorn; Moenter, Suzanne M

    2018-01-01

    Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

  10. Spin-dependent and photon-assisted transmission enhancement and suppression in a magnetic-field tunable ZnSe/Zn{sub 1–x}Mn{sub x}Se heterostructure

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chun-Lei, E-mail: licl@cnu.edu.cn [Laboratory for Micro-sized Functional Materials, College of Elementary Education, Capital Normal University, Beijing 100048 (China); Department of Physics and State Key Laboratory of Low-Dimensional Quantum Physics, Tsinghua University, Beijing 100084 (China); Yuan, Rui-Yang [Center for Theoretical Physics, Department of Physics, Capital Normal University, Beijing 100048 (China); Guo, Yong, E-mail: guoy66@tsinghua.edu.cn [Department of Physics and State Key Laboratory of Low-Dimensional Quantum Physics, Tsinghua University, Beijing 100084 (China); Collaborative Innovation Center of Quantum Matter, Beijing (China)

    2016-01-07

    Using the effective-mass approximation and Floquet theory, we theoretically investigate the terahertz photon-assisted transport through a ZnSe/Zn{sub 1−x}Mn{sub x}Se heterostructure under an external magnetic field, an electric field, and a spatially homogeneous oscillatory field. The results show that both amplitude and frequency of the oscillatory field can accurately manipulate the magnitude of the spin-dependent transmission probability and the positions of the Fano-type resonance due to photon absorption and emission processes. Transmission resonances can be enhanced to optimal resonances or drastically suppressed for spin-down electrons tunneling through the heterostructure and for spin-up ones tunneling through the same structure, resonances can also be enhanced or suppressed, but the intensity is less than the spin-down ones. Furthermore, it is important to note that transmission suppression can be clearly seen from both the spin-down component and the spin-up component of the current density at low magnetic field; at the larger magnetic field, however, the spin-down component is suppressed, and the spin-up component is enhanced. These interesting properties may provide an alternative method to develop multi-parameter modulation electron-polarized devices.

  11. Synthetic triterpenoid induces 15-PGDH expression and suppresses inflammation-driven colon carcinogenesis.

    Science.gov (United States)

    Choi, Sung Hee; Kim, Byung-Gyu; Robinson, Janet; Fink, Steve; Yan, Min; Sporn, Michael B; Markowitz, Sanford D; Letterio, John J

    2014-06-01

    Colitis-associated colon cancer (CAC) develops as a result of inflammation-induced epithelial transformation, which occurs in response to inflammatory cytokine-dependent downregulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and subsequent suppression of prostaglandin metabolism. Agents that both enhance 15-PGDH expression and suppress cyclooxygenase-2 (COX-2) production may more effectively prevent CAC. Synthetic triterpenoids are a class of small molecules that suppress COX-2 as well as inflammatory cytokine signaling. Here, we found that administration of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-C28-methyl ester (CDDO-Me) suppresses CAC in mice. In a spontaneous, inflammation-driven intestinal neoplasia model, deletion of Smad4 specifically in T cells led to progressive production of inflammatory cytokines, including TNF-α, IFN-γ, iNOS, IL-6, IL-1β; as well as activation of STAT1 and STAT3; along with suppression of 15-PGDH expression. Oral administration of CDDO-Me to mice with SMAD4-deficient T cells increased survival and suppressed intestinal epithelial neoplasia by decreasing production of inflammatory mediators and increasing expression of 15-PGDH. Induction of 15-PGDH by CDDO-Me was dose dependent in epithelial cells and was abrogated following treatment with TGF-β signaling inhibitors in vitro. Furthermore, CDDO-Me-dependent 15-PGDH induction was not observed in Smad3-/- mice. Similarly, CDDO-Me suppressed azoxymethane plus dextran sodium sulfate-induced carcinogenesis in wild-type animals, highlighting the potential of small molecules of the triterpenoid family as effective agents for the chemoprevention of CAC in humans.

  12. Impact of Room Location on UV-C Irradiance and UV-C Dosage and Antimicrobial Effect Delivered by a Mobile UV-C Light Device.

    Science.gov (United States)

    Boyce, John M; Farrel, Patricia A; Towle, Dana; Fekieta, Renee; Aniskiewicz, Michael

    2016-06-01

    OBJECTIVE To evaluate ultraviolet C (UV-C) irradiance, UV-C dosage, and antimicrobial effect achieved by a mobile continuous UV-C device. DESIGN Prospective observational study. METHODS We used 6 UV light sensors to determine UV-C irradiance (W/cm2) and UV-C dosage (µWsec/cm2) at various distances from and orientations relative to the UV-C device during 5-minute and 15-minute cycles in an ICU room and a surgical ward room. In both rooms, stainless-steel disks inoculated with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Clostridium difficile spores were placed next to sensors, and UV-C dosages and log10 reductions of target organisms achieved during 5-minute and 15-minute cycles were determined. Mean irradiance and dosage readings were compared using ANOVA. RESULTS Mean UV-C irradiance was nearly 1.0E-03 W/cm2 in direct sight at a distance of 1.3 m (4 ft) from the device but was 1.12E-05 W/cm2 on a horizontal surface in a shaded area 3.3 m (10 ft) from the device (P4 to 1-3 for MRSA, >4 to 1-2 for VRE and >4 to 0 log10 for C. difficile spores, depending on the distance from, and orientation relative to, the device with 5-minute and 15-minute cycles. CONCLUSION UV-C irradiance, dosage, and antimicrobial effect received from a mobile UV-C device varied substantially based on location in a room relative to the UV-C device. Infect Control Hosp Epidemiol 2016;37:667-672.

  13. Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2016-07-25

    At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

  14. The dependence of the anomalous $J/\\psi$ suppression on the number of participant nucleons

    CERN Document Server

    Abreu, M C; Alexa, C; Arnaldi, R; Ataian, M R; Baglin, C; Baldit, A; Bedjidian, Marc; Beolè, S; Boldea, V; Bordalo, P; Borges, G; Bussière, A; Capelli, L; Castor, J I; Castanier, C; Chaurand, B; Chevrot, I; Cheynis, B; Chiavassa, E; Cicalò, C; Claudino, T; Comets, M P; Constans, N; Constantinescu, S; Cortese, P; De Marco, N; De Falco, A; Dellacasa, G; Devaux, A; Dita, S; Drapier, O; Ducroux, L; Espagnon, B; Fargeix, J; Force, P; Gallio, M; Gavrilov, Yu K; Gerschel, C; Giubellino, P; Golubeva, M B; Gonin, M; Grigorian, A A; Grigorian, S; Grossiord, J Y; Guber, F F; Guichard, A; Gulkanian, H R; Hakobyan, R S; Haroutunian, R; Idzik, M; Jouan, D; Karavitcheva, T L; Kluberg, L; Kurepin, A B; Le Bornec, Y; Lourenço, C; Macciotta, P; MacCormick, M; Marzari-Chiesa, A; Masera, M; Masoni, A; Monteno, M; Musso, A; Petiau, P; Piccotti, A; Pizzi, J R; Prino, F; Puddu, G; Quintans, C; Ramos, S; Ramello, L; Rato-Mendes, P; Riccati, L; Romana, A; Santos, H; Saturnini, P; Scalas, E; Scomparin, E; Serci, S; Shahoyan, R; Sigaudo, F; Silva, S; Sitta, M; Sonderegger, P; Tarrago, X; Topilskaya, N S; Usai, G L; Vercellin, Ermanno; Villatte, L; Willis, N

    2001-01-01

    The observation of an anomalous \\jpsi\\ suppression in \\mbox{Pb-Pb} collisions by the NA50 collaboration can be considered as the most striking indication for the deconfinement of quarks and gluons at SPS energies. In this letter, we determine the \\jpsi\\ suppression pattern as a function of the forward hadronic energy \\ezdc\\ measured in a Zero Degree Calorimeter (ZDC). The direct connection between \\ezdc\\ and the geometry of the collision allows us to calculate, within a Glauber approach, the precise relation between the number of participant nucleons \

  15. Dual effects of N-acetyl-L-cysteine dependent on NQO1 activity: Suppressive or promotive of 9,10-phenanthrenequinone-induced toxicity

    International Nuclear Information System (INIS)

    Toyooka, Tatsushi; Shinmen, Takuya; Aarts, Jac M.M.J.G.; Ibuki, Yuko

    2012-01-01

    A typical antioxidant, N-acetyl-L-cysteine (NAC) generally protects cells from oxidative damage induced by reactive oxygen species (ROS). 9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, produces ROS in redox cycling following two-electron reduction by NAD(P)H:quinone oxidoreductase 1 (NQO1), which has been considered as a cause of its cyto- and genotoxicity. In this study, we show that NAC unexpectedly augments the toxicity of 9,10-PQ in cells with low NQO1 activity. In four human skin cell lines, the expression and the activity of NQO1 were lower than in human adenocarcinoma cell lines, A549 and MCF7. In the skin cells, the cytotoxicity of 9,10-PQ was significantly enhanced by addition of NAC. The formation of DNA double strand breaks accompanying phosphorylation of histone H2AX, was also remarkably augmented. On the other hand, the cyto- and genotoxicity were suppressed by addition of NAC in the adenocarcinoma cells. Two contrasting experiments: overexpression of NQO1 in CHO-K1 cells which originally expressed low NQO1 levels, and knock‐down of NQO1 in the adenocarcinoma cell line A549 by transfection of RNAi, also showed that NAC suppressed 9,10-PQ-induced toxicity in cell lines expressing high NQO1 activity and enhanced it in cell lines with low NQO1 activity. The results suggested that dual effects of NAC on the cyto- and genotoxicity of 9,10-PQ were dependent on tissue-specific NQO1 activity. -- Highlights: ► NAC augmented the cytotoxicity of 9,10-PQ in skin cell lines. ► 9,10-PQ-induced DSBs accompanying γ-H2AX were also augmented by NAC. ► NAC suppressed the cyto- and genotoxicity of 9,10-PQ in adenocarcinoma cell lines. ► The dual effects of NAC on toxicity of 9,10-PQ were dependent on NQO1 activity.

  16. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners.

    Directory of Open Access Journals (Sweden)

    Sandra A Springer

    Full Text Available HIV-infected prisoners lose viral suppression within the 12 weeks after release to the community. This prospective study evaluates the use of buprenorphine/naloxone (BPN/NLX as a method to reduce relapse to opioid use and sustain viral suppression among released HIV-infected prisoners meeting criteria for opioid dependence (OD.From 2005-2010, 94 subjects meeting DSM-IV criteria for OD were recruited from a 24-week prospective trial of directly administered antiretroviral therapy (DAART for released HIV-infected prisoners; 50 (53% selected BPN/NLX and were eligible to receive it for 6 months; the remaining 44 (47% selected no BPN/NLX therapy. Maximum viral suppression (MVS, defined as HIV-1 RNA<50 copies/mL, was compared for the BPN/NLX and non-BPN/NLX (N = 44 groups.The two groups were similar, except the BPN/NLX group was significantly more likely to be Hispanic (56.0% v 20.4%, from Hartford (74.4% v 47.7% and have higher mean global health quality of life indicator scores (54.18 v 51.40. MVS after 24 weeks of being released was statistically correlated with 24-week retention on BPN/NLX [AOR = 5.37 (1.15, 25.1], having MVS at the time of prison-release [AOR = 10.5 (3.21, 34.1] and negatively with being Black [AOR = 0.13 (0.03, 0.68]. Receiving DAART or methadone did not correlate with MVS.In recognition that OD is a chronic relapsing disease, strategies that initiate and retain HIV-infected prisoners with OD on BPN/NLX is an important strategy for improving HIV treatment outcomes as a community transition strategy.

  17. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Nathella Pavan Kumar

    Full Text Available Although Type 1 cytokine responses are considered protective in pulmonary tuberculosis (PTB, their role as well as those of Type 2, 17 and immunoregulatory cytokines in tuberculous lymphadenitis (TBL and latent tuberculosis (LTB have not been well studied.To identify cytokine responses associated with pulmonary tuberculosis (TB, TB lymphadenitits and latent TB, we examined mycobacterial antigen-specific immune responses of PTB, TBL and LTB individuals. More specifically, we examined ESAT-6 and CFP-10 induced Type 1, Type 2 and Type 17 cytokine production and their regulation using multiplex ELISA.PTB individuals exhibited a significantly lower baseline as well as antigen-specific production of Type 1 (IFNγ, TNFα and IL-2; Type 2 (IL-4 and Type 17 (IL-17A and IL-17F cytokines in comparison to both TBL and LTB individuals. TBL individuals exhibited significantly lower antigen-specific IFNγ responses alone in comparison to LTB individuals. Although, IL-10 levels were not significantly higher, neutralization of IL-10 during antigen stimulation resulted in significantly enhanced production of IFNγ, IL-4 and IL-17A in PTB individuals, indicating that IL-10 mediates (at least partially the suppression of cytokine responses in PTB.Pulmonary TB is characterized by an IL-10 dependent antigen-specific suppression of Type 1, Type 2 and Type 17 cytokines, reflecting an important association of these cytokines in the pathogenesis of active TB.

  18. Volcanic ash dosage calculator: A proof-of-concept tool to support aviation stakeholders during ash events

    Science.gov (United States)

    Dacre, H.; Prata, A.; Shine, K. P.; Irvine, E.

    2017-12-01

    The volcanic ash clouds produced by Icelandic volcano Eyjafjallajökull in April/May 2010 resulted in `no fly zones' which paralysed European aircraft activity and cost the airline industry an estimated £1.1 billion. In response to the crisis, the Civil Aviation Authority (CAA), in collaboration with Rolls Royce, produced the `safe-to-fly' chart. As ash concentrations are the primary output of dispersion model forecasts, the chart was designed to illustrate how engine damage progresses as a function of ash concentration. Concentration thresholds were subsequently derived based on previous ash encounters. Research scientists and aircraft manufactures have since recognised the importance of volcanic ash dosages; the accumulated concentration over time. Dosages are an improvement to concentrations as they can be used to identify pernicious situations where ash concentrations are acceptably low but the exposure time is long enough to cause damage to aircraft engines. Here we present a proof-of-concept volcanic ash dosage calculator; an innovative, web-based research tool, developed in close collaboration with operators and regulators, which utilises interactive data visualisation to communicate the uncertainty inherent in dispersion model simulations and subsequent dosage calculations. To calculate dosages, we use NAME (Numerical Atmospheric-dispersion Modelling Environment) to simulate several Icelandic eruption scenarios, which result in tephra dispersal across the North Atlantic, UK and Europe. Ash encounters are simulated based on flight-optimal routes derived from aircraft routing software. Key outputs of the calculator include: the along-flight dosage, exposure time and peak concentration. The design of the tool allows users to explore the key areas of uncertainty in the dosage calculation and to visualise how this changes as the planned flight path is varied. We expect that this research will result in better informed decisions from key stakeholders during

  19. Digital and conventional radiology techniques: comparison of dosage and costs

    International Nuclear Information System (INIS)

    Arranza, L.; Albornoz, C. de

    1996-01-01

    To compare the radiation dosage and costs in conventional and digital technologies. The study dealt with transverse sections. The dosage applied with conventional technology was measured in 254 patients who intertwined 402 explorations of 6 anatomic regions in 4 Radiodiagnostic Services. The dosage applied with digital technology was measured in 57 patients who underwent 95 explorations of the same anatomic region in one Radiodiagnostic Service. The costs of the 6 types of conventional and digital explorations performed were calculated for two Radiodiagnostic Service. The doses administered (mGy) using convectional/digital technology were as follows: chest PA 0.2/0.1; chest LAT 0.7/0.3; breast CC 7.0/8.4; breast LAT 7.0/7.8; breast OB 7.0/10.5; cervical spine AP 9.6/9.0; cervical spine LAT 21.9/29.6; pelvis AP 7.3/7.1; plain abdominal 6.5/2.2. The costs incurred (1992 pesetas) with the convectional/digital technologies: chest AP and LAT 1,393/2,973; portable chest 2,027/3,714; mammography 2,357/3,486; phlebography 12,718/14,023; hysterosalpingography 4,876/6,701; bone scientigraphy 1,633/2,839. Compared with conventional technology, digital imaging reduces the radiation doses received by the patients, except in the case of mammography. The costs associated with the use of digital technology are greater than those incurred with conventional technology, mainly due to the costs of amortization. the use of digital technology is more justified when: 1) it is very necessary to reduce the dosage; 2) studies of chest and abdomen predominant; 3) the volume of utilization is high; 4) staff management is flexible , and 5) the cost of purchasing the equipment is lower. (Author) 10 refs

  20. Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study.

    Science.gov (United States)

    de la Torre, Inmaculada; Valor, Lara; Nieto, Juan Carlos; Montoro, María; Carreño, Luis

    2014-01-01

    To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition to 36 newborn infants using a dosage schedule

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Andersen, G E

    1984-01-01

    Ampicillin and gentamicin were given continuously i.v. to 36 newborn infants using a dosage schedule and the results were compared with those obtained in an earlier study including 88 infants who received individually calculated dosages. With the dosage schedule the variation in the serum concent...

  2. Effects of pharmaceutical processing on pepsin activity during the formulation of solid dosage forms.

    Science.gov (United States)

    Kristó, Katalin; Pintye-Hódi, Klára

    2013-02-01

    The main aim of this study was to investigate the effects of pharmaceutical technological methods on pepsin activity during the formulation of solid dosage forms. The circumstances of direct compression and wet granulation were modeled. During direct compression, the heat and the compression force must be taken into consideration. The effects of these parameters were investigated in three materials (pure pepsin, and 1:1 (w/w) pepsin-tartaric acid and 1:1 (w/w) pepsin-citric acid powder mixtures). It was concluded that direct compression is appropriate for the formulation of solid dosage forms containing pepsin through application without acids or with acids at low compression force. The effects of wet granulation were investigated with a factorial design for the same three materials. The factors were time, temperature and moisture content. There was no significant effect of the factors when acids were not applied. Temperature was a significant factor when acids were applied. The negative effect was significantly higher for citric acid than for tartaric acid. It was found that wet granulation can be utilized for the processing of pepsin into solid dosage forms under well-controlled circumstances. The application of citric acid is not recommended during the formulation of solid dosage forms through wet granulation. A mathematically based optimization may be necessary for preformulation studies of the preparation of dosage forms containing sensitive enzymes.

  3. 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

    Science.gov (United States)

    Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2018-01-30

    It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry.

    Science.gov (United States)

    Lin, Amy; Ching, Christopher R K; Vajdi, Ariana; Sun, Daqiang; Jonas, Rachel K; Jalbrzikowski, Maria; Kushan-Wells, Leila; Pacheco Hansen, Laura; Krikorian, Emma; Gutman, Boris; Dokoru, Deepika; Helleman, Gerhard; Thompson, Paul M; Bearden, Carrie E

    2017-06-28

    Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in subregions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development. SIGNIFICANCE STATEMENT Probing naturally occurring reciprocal copy number variation in the genome may help us understand mechanisms underlying deviations from typical brain and cognitive development. The 22q11.2 genomic region is particularly susceptible to chromosomal rearrangements and contains many genes crucial for neuronal development and migration. Not surprisingly

  5. Prevalence and trends of cellulosics in pharmaceutical dosage forms.

    Science.gov (United States)

    Mastropietro, David J; Omidian, Hossein

    2013-02-01

    Many studies have shown that cellulose derivatives (cellulosics) can provide various benefits when used in virtually all types of dosage forms. Nevertheless, the popularity of their use in approved drug products is rather unknown. This research reports the current prevalence and trends of use for 15 common cellulosics in prescription drug products. The cellulosics were powdered and microcrystalline cellulose (MCC), ethyl cellulose, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hypromellose (HPMC), HPMC phthalate, HPMC acetate succinate, cellulose acetate (CA), CA phthalate, sodium (Na) and calcium (Ca) carboxymethylcellulose (CMC), croscarmellose sodium (XCMCNa), methyl cellulose, and low substituted HPC. The number of brand drug products utilizing each cellulosics was determined using the online drug index Rxlist. A total of 607 brand products were identified having one or more of the cellulosics as an active or inactive ingredient. An array of various dosage forms was identified and revealed HPMC and MCC to be the most utilized cellulosics in all products followed by XCMCNa and HPC. Many products contained two or more cellulosics in the formulation (42% containing two, 23% containing three, and 4% containing 4-5). The largest combination occurrence was HPMC with MCC. The use of certain cellulosics within different dosage form types was found to contain specific trends. All injectables utilized only CMCNa, and the same with all ophthalmic solutions utilizing HPMC, and otic suspensions utilizing HEC. Popularity and trends regarding cellulosics use may occur based on many factors including functionality, safety, availability, stability, and ease of manufacturing.

  6. Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

    Science.gov (United States)

    Al-Gousous, Jozef; Langguth, Peter

    2016-02-01

    To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. Saponarin activates AMPK in a calcium-dependent manner and suppresses gluconeogenesis and increases glucose uptake via phosphorylation of CRTC2 and HDAC5.

    Science.gov (United States)

    Seo, Woo-Duck; Lee, Ji Hae; Jia, Yaoyao; Wu, Chunyan; Lee, Sung-Joon

    2015-11-15

    This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did not directly interact with the AMPK protein. Instead, saponarin increased intracellular calcium levels and induced AMPK phosphorylation, which was diminished by co-stimulation with STO-609, an inhibitor of CAMKKβ. Transcription of hepatic gluconeogenesis genes was upregulated by nuclear translocation of CRTC2 and HDAC5, coactivators of CREB and FoxO1 transcription factors, respectively. This nuclear translocation was inhibited by increased phosphorylation of CRTC2 and HDAC5 by saponarin-induced AMPK in HepG2 cells and suppression of CREB and FoxO1 transactivation activities in cells stimulated by saponarin. The results from a chromatin immunoprecipitation assay confirmed the reduced binding of CRTC2 on the PEPCK and G6Pase promoters. In TE671 cells, AMPK phosphorylated HDAC5, which suppressed nuclear penetration and upregulated GLUT4 transcription, leading to enhanced glucose uptake. Collectively, these results suggest that saponarin activates AMPK in a calcium-dependent manner, thus regulating gluconeogenesis and glucose uptake. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. The effect of dosages of microbial consortia formulation and synthetic fertilizer on the growth and yield of field-grown chili

    Science.gov (United States)

    Istifadah, N.; Sapta, D.; Krestini, H.; Natalie, B.; Suryatmana, P.; Nurbaity, A.; Hidersah, R.

    2018-03-01

    Chili (Capsicum annuum, L) is one of important horticultural crop in Indonesia. Formulation of microbial consortia containing Bacillus subtilis, Pseudomonas sp., Azotobacter chroococcum and Trichoderma harzianum has been developed. This study evaluated the effects of dosage of the microbial formulation combined with NPK fertilizer on growth and yield of chili plants in the field experiment. The experiment was arranged in completely randomized design of factorial, in which the first factor was dosage of formulation (0, 2.5, 5.0, 7.5, 10 g per plant) and the second factor was NPK fertilizer dosage (0, 25, 50 and 75% of the standard dosage). The treatments were replicated three times. For application, the formulation was mixed with chicken manure 1:10 (w/v). The results showed that application of microbial formulation solely improved the chili growth. There was interaction between dosages of the microbial formulation and NPK fertilizer in improving plant height, nitrogen availability and the chili yield, while there was no interaction between those dosages in improving the root length. Combination between microbial formulation at the dosage of 5.0-7.5 g per plant combined with NPK fertilizer with the dosage 50 or 75% of the standard dosage support relatively better growth and the chili yield.

  9. Rb suppresses collective invasion, circulation and metastasis of breast cancer cells in CD44-dependent manner.

    Directory of Open Access Journals (Sweden)

    Kui-Jin Kim

    Full Text Available Basal-like breast carcinomas (BLCs present with extratumoral lymphovascular invasion, are highly metastatic, presumably through a hematogenous route, have augmented expression of CD44 oncoprotein and relatively low levels of retinoblastoma (Rb tumor suppressor. However, the causal relation among these features is not clear. Here, we show that Rb acts as a key suppressor of multiple stages of metastatic progression. Firstly, Rb suppresses collective cell migration (CCM and CD44-dependent formation of F-actin positive protrusions in vitro and cell-cluster based lymphovascular invasion in vivo. Secondly, Rb inhibits the release of single cancer cells and cell clusters into the hematogenous circulation and subsequent metastatic growth in lungs. Finally, CD44 expression is required for collective motility and all subsequent stages of metastatic progression initiated by loss of Rb function. Altogether, our results suggest that Rb/CD44 pathway is a crucial regulator of CCM and metastatic progression of BLCs and a promising target for anti-BLCs therapy.

  10. Histomorphological study of submandibulary glands of rats submitted to low dosage of X-radiation

    International Nuclear Information System (INIS)

    Navarro, Claudia Maria; Onofre, Mirian Aparecida; Chan, Carolina; Cordeiro, Rita de Cassis Loiola; Raveli, Dirceu Barnabe

    1996-01-01

    The minimal dosage of X-ray that is likely to induce cellular alterations is unknown and there are just a few reports with low dosage in odontologic literature. The authors developed a histomorphological analysis of the submandibulary glands of rat that received low dosage of X radiation. The body of the animals was covered with a lead lamin leaving the cervical area uncovered. The submandibular glands were exposed to 1,80 Gy of X-radiation in a single dose. After 24, 48, 72 hours, 7, 14 and 21 days the glands were excised, fixed and prepared for analysis in light microscopy. Mild degenerative changes and nuclear pleomorfism, mainly on the first three experimental periods were observed. (author)

  11. 21 CFR 520.1448 - Monensin oral dosage forms.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... distance the spots travel from the starting line divided by the distance the solvent front travels from the...

  12. TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription.

    Science.gov (United States)

    Gómez-Herreros, Fernando; Zagnoli-Vieira, Guido; Ntai, Ioanna; Martínez-Macías, María Isabel; Anderson, Rhona M; Herrero-Ruíz, Andrés; Caldecott, Keith W

    2017-08-10

    DNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation 'hotspot', MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability.DNA double-strand breaks (DSBs) induced by topoisomerase II (TOP2) are rejoined by TDP2-dependent non-homologous end-joining (NHEJ) but whether this promotes or suppresses translocations is not clear. Here the authors show that TDP2 suppresses chromosome translocations from DSBs introduced during gene transcription.

  13. Estimated Effect of Epoetin Dosage on Survival among Elderly Hemodialysis Patients in the United States

    OpenAIRE

    Zhang, Yi; Thamer, Mae; Cotter, Dennis; Kaufman, James; Hernán, Miguel A.

    2009-01-01

    Background and objectives: The common finding that low achieved hemoglobin in observational studies and high target hemoglobin in randomized trials each were associated with increased mortality and high epoetin dosage has suggested the possibility that high epoetin dosage might explain the increased mortality risk.

  14. Iron oxide magnetic nanoparticles combined with actein suppress non-small-cell lung cancer growth in a p53-dependent manner

    Directory of Open Access Journals (Sweden)

    Wang MS

    2017-10-01

    Full Text Available Ming-Shan Wang,1 Liang Chen,2 Ya-Qiong Xiong,2 Jing Xu,2 Ji-Peng Wang,2 Zi-Li Meng2 1Department of Oncology, Huaiyin Hospital of Huai’an City, Huai’an, China; 2Department of Respiration, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China Abstract: Actein (AT is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida that has been investigated for its antitumor effects. AT treatment leads to apoptosis in various cell types, including breast cancer cells, by regulating different signaling pathways. Iron oxide (Fe3O4 magnetic nanoparticles (MNPs are nanomaterials with biocompatible activity and low toxicity. In the present study, the possible benefits of AT in combination with MNPs on non-small-cell lung cancer (NSCLC were explored in in vitro and in vivo studies. AT-MNP treatment contributed to apoptosis in NSCLC cells, as evidenced by activation of the caspase 3-signaling pathway, which was accompanied by downregulation of the antiapoptotic proteins Bcl2 and BclXL, and upregulation of the proapoptotic signals Bax and Bad. The death receptors of TRAIL were also elevated following AT-MNP treatment in a p53-dependent manner. Furthermore, a mouse xenograft model in vivo revealed that AT-MNP treatment exhibited no toxicity and suppressed NSCLC growth compared to either AT or MNP monotherapies. In conclusion, this study suggests a novel therapy to induce apoptosis in suppressing NSCLC growth in a p53-dependent manner by combining AT with Fe3O4 MNPs. Keywords: actein, Fe3O4 magnetic nanoparticles, NSCLC, apoptosis, p53

  15. Transverse momentum dependence of J/Ψsuppression in an equilibrium hadron gas

    International Nuclear Information System (INIS)

    Prorok, D.; Turko, L.

    1994-01-01

    We consider an ideal gas of massive hadrons in thermal and chemical equilibrium. The gas expands longitudinally in accordance with the Bjorken law. We show that J/Ψ suppression such an environment is essentially the same as in a pion gas of the equal initial energy density and agrees with the NA38 data. (orig.)

  16. Hyperintense acute reperfusion marker is associated with higher contrast agent dosage in acute ischaemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Ostwaldt, Ann-Christin; Schaefer, Tabea; Villringer, Kersten; Fiebach, Jochen B. [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Rozanski, Michal; Ebinger, Martin [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Charite Universitaetsmedizin, Department of Neurology, Berlin (Germany); Jungehuelsing, Gerhard J. [Stiftung des Buergerlichen Rechts, Juedisches Krankenhaus Berlin, Berlin (Germany)

    2015-11-15

    The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients. We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images. HARM was detected in 97 patients (18.3 %). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation. A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages. (orig.)

  17. Adrenal Insufficiency under Standard Dosage of Glucocorticoid Replacement after Unilateral Adrenalectomy for Cushing’s Syndrome

    Directory of Open Access Journals (Sweden)

    Kentaro Fujii

    2016-01-01

    Full Text Available Glucocorticoid replacement is needed for patients after adrenal surgery for Cushing’s syndrome; however, the adequate dosage is not easily determined. The patient was a 62-year-old woman who has had hypertension for 5 years and presented with heart failure due to hypertrophic cardiomyopathy. She consulted with us because of general fatigue, facial edema, and muscle weakness and was diagnosed with Cushing’s syndrome. A laparoscopic left adrenalectomy was performed, standard dosage of postoperative replacement was administered, and she was discharged with 30 mg/day of hydrocortisone (cortisol. However, she suffered from loss of appetite and was transferred to an emergency unit with the symptoms of adrenal insufficiency on postoperative day 15. After initial hydrocortisone replacement with 200 mg/day, the dosage was gradually decreased during hospitalization; however, reduction of hydrocortisone dosage lower than 60 mg/day was difficult because of nausea and fatigue. Her circadian cortisol profile after hydrocortisone administration showed delayed and lowered peaks, which suggested that hydrocortisone absorption in the intestine was impaired. Therefore, complicated heart failure may have led to the adrenal insufficiency in the patient. In such cases, we should consider postoperative administration of more than the standard dosage of hydrocortisone to avoid adrenal insufficiency after surgery for Cushing’s syndrome.

  18. Dosage Parameters in Pediatric Outcome Studies Reported in 9 Peer-Reviewed Occupational Therapy Journals from 2008 to 2014: A Content Analysis

    Science.gov (United States)

    Gee, Bryan M.; Lloyd, Kimberly; Devine, Nancy; Tyrrell, Erin; Evans, Trisha; Hill, Rebekah; Dineen, Stacee; Magalogo, Kristin

    2016-01-01

    Occupational therapists determine the dosage when establishing the plan of care for their pediatric clients. A content analysis was conducted using 123 pediatric occupational therapy outcomes studies from 9 scholarly international occupational therapy journals. The parameters of dosage were calculated using descriptive statistics in order to obtain a representation of dosage available within the current collage of pediatric occupational therapy outcomes studies. The results revealed that most studies reported portions of dosage parameters within the published studies. The average findings for the subcomponents related to dosage were session length (minutes) M = 58.7, duration of plan of care (weeks) M = 12.1, session frequency (per week) M = 3.4, and total hours of therapy (hours) M = 18.1. This first attempt at describing and calculating dosage related to pediatric occupational therapy practice indicates that evidence is lacking within the published literature to adequately guide OT dosage decisions. Further research related to dosage in pediatric occupational therapy practice is needed. PMID:26949547

  19. Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism.

    Science.gov (United States)

    Li, Jianchang; Qiu, Mingning; Chen, Lieqian; Liu, Lei; Tan, Guobin; Liu, Jianjun

    2017-02-01

    The aim of the present study was to investigate the effect of resveratrol on renal carcinoma cells and explore possible renin-angiotensin system-associated mechanisms. Subsequent to resveratrol treatment, the cell viability, apoptosis rate, cytotoxicity levels, caspase 3/7 activity and the levels of angiotensin II (AngII), AngII type 1 receptor (AT1R), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were evaluated in renal carcinoma cells. The effects of AngII, AT1R, VEGF and COX-2 on resveratrol-induced cell growth inhibition and apoptosis were also examined. The results indicated that resveratrol treatment may suppress growth, induce apoptosis, and decrease AngII, AT1R, VEGF and COX-2 levels in renal carcinoma ACHN and A498 cells. In addition, resveratrol-induced cell growth suppression and apoptosis were reversed when co-culturing with AT1R or VEGF. Thus, resveratrol may suppress renal carcinoma cell proliferation and induce apoptosis via an AT1R/VEGF pathway.

  20. The characteristics of novel dosage forms

    Directory of Open Access Journals (Sweden)

    Milić-Aškrabić Jela

    2003-01-01

    Full Text Available The objective of pharmaceutical-technological development is to find a procedure of transforming an active substance (a drug into a drug dosage form which is not only acceptable for application, but also enables the active substance to be released following administration, pursuant to therapy objectives. The aim is that the concentration of the active substance in the action location rapidly reaches a therapeutic level and maintains an approximately constant level in the course of a particular time, according to the established therapeutic goal. The primary objective is to present the active ingredient (drug in the form and concentration/quantity that enables the corresponding therapeutic response, i.e. to control the site and rate of medicinal substance release from the drug, as well as the rate at which it reaches the membranes and surfaces to which it is absorbed, while applying a common method of administration. The procedures used to achieve this goal are becoming highly complex and demanding and are aiming at sophisticated drug delivery systems and functional packaging material. Development from the existing drug molecule, through the conventional drug dosage form, to a new system of drug "delivery" (novel delivery system, can improve the drug (active substance characteristics significantly in view of compliance (acceptability by the patient, safety and efficiency. The paper presents an overview of the most important examples of pharmaceutical forms with controlled release and advanced drug "carriers".

  1. Dosage of DTPA administration by inhalation

    International Nuclear Information System (INIS)

    Koizumi, Akira; Fukuda, Satoshi; Yamada, Yuji; Iida, Haruzo; Shimo, Michikuni

    2000-01-01

    The administration of DTPA by inhalation was examined as an emergency medical treatment. In order to estimate the practical dosage to the human, an accurate model of the human air way was connected to a anesthetizer and respiration was simulated. Ca-DTPA, aerosolized by an ultra-sonic nebulizer, was administered by inhalation to the model. For the experiments, the respiratory volume (tidal volume) and the respiration rate was 12 per minute. Irrigation water from the model of larynx and mouth, and the air filter were collected and measured by chelate titration in order to determine the quantity of aerosolized DTPA and the amount deposited on the trachea and lang. The results indicated that the quantity of aerosolized DTPA varied with dilution of the DTPA solution in a ample. It was found that a 3 time dilution was the most practical and that 73 mg of DTPA per minute could be aerosolized. Furthermore, the results indicated that 46% of the aerosolized DTPA was taken in through inhalation and that 26% of DTPA was deposited in the trachea and lung. These results suggest that in practical application in the emergency medical treatment, 15 minutes of inhalation could delivered to approximately 500 mg of DTPA, and 130 mg could be delivered to the trachea and lung. It is considered that these quantity are enough amount to increase the effects of radioactive nuclides from the body, comparing with the recommended dosage for injection administration. (author)

  2. Dosage of strontium 90 in human bone ashes; Dosage du strontium 90 sans les cendres d'os humain

    Energy Technology Data Exchange (ETDEWEB)

    Patti, F; Jeanmaire, L [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1964-07-01

    The determination of {sup 90}Sr in bones by dosage of its daughter product {sup 90}Y is a 4-step process: 1) elimination of the phosphate ions by precipitation of the Ca and Sr as oxalate in the presence of acid; 2) reduction in the calcium concentration to a suitable level by the addition of a known volume of nitric acid (a single precipitation is sufficient), the precipitation yield of the strontium nitrate is checked by the measurement of the amount of {sup 85}Sr added as tracer; 3) purification by a yttrium hydroxide precipitation; 4) extraction at equilibrium of the {sup 90}Y which is counted to give the concentration. By using 50 gm of ash it is possible to detect about 0.1 pCi of {sup 90}Sr per gram of calcium. The advantages of this technique: -) treatment of a large quantity of bone ash -) the use of a small volume of nitric acid (less than 2 ml/g of ash, and -) the various operations present no difficulty. (authors) [French] Determination du Sr dans les os par dosage de son produit de filiation {sup 90}Y. Principe du dosage: 1 - Eliminer les ions phosphates par precipitation du calcium et du strontium sous forme d'oxalate en milieu acide. 2 - Reduire la concentration en calcium a un niveau convenable par addition d'un volume determine d'acide nitrique (une seule precipitation est necessaire). Le rendement de precipitation du nitrate de strontium est controle par la mesure de {sup 85}Sr ajoute comme traceur. 3 - Purifier par une precipitation d'hydroxyde d'yttrium. 4 - Extraire a l'equilibre l'{sup 90}Y qui eat compte pour determiner le {sup 90}Sr. En traitant 50 g de cendre, il est possible de deceler de l'ordre de 0,1 pCi de {sup 90}Sr par gramme de calcium. Les 3 avantages de cette technique: 1 - traitement d'une quantite importante de cendres d'os, 2 - emploi d'un faible volume d'acide nitrique (moins de 2 ml/g de cendres), et 3 - les diverses operations ne presentent aucune difficulte.

  3. C. elegans FOG-3/Tob can either promote or inhibit germline proliferation, depending on gene dosage and genetic context.

    Science.gov (United States)

    Snow, J J; Lee, M-H; Verheyden, J; Kroll-Conner, P L; Kimble, J

    2013-05-23

    Vertebrate Tob/BTG proteins inhibit cell proliferation when overexpressed in tissue-culture cells, and they can function as tumor suppressors in mice. The single Caenorhabditis elegans Tob/BTG ortholog, FOG-3, by contrast, was identified from its loss-of-function phenotype as a regulator of sperm fate specification. Here we report that FOG-3 also regulates proliferation in the germline tissue. We first demonstrate that FOG-3 is a positive regulator of germline proliferation. Thus, fog-3 null mutants possess fewer germ cells than normal, a modest but reproducible decrease observed for each of two distinct fog-3 null alleles. A similar decrease also occurred in fog-3/+ heterozygotes, again for both fog-3 alleles, revealing a haplo-insufficient effect on proliferation. Therefore, FOG-3 normally promotes proliferation, and two copies of the fog-3 gene are required for this function. We next overexpressed FOG-3 by removal of FBF, the collective term for FBF-1 and FBF-2, two nearly identical PUF RNA-binding proteins. We find that overexpressed FOG-3 blocks proliferation in fbf-1 fbf-2 mutants; whereas germ cells stop dividing and instead differentiate in fbf-1 fbf-2 double mutants, they continue to proliferate in fog-3; fbf-1 fbf-2 triple mutants. Therefore, like its vertebrate Tob/BTG cousins, overexpressed FOG-3 is 'antiproliferative'. Indeed, some fog-3; fbf-1 fbf-2 mutants possess small tumors, suggesting that FOG-3 can act as a tumor suppressor. Finally, we show that FOG-3 and FBF work together to promote tumor formation in animals carrying oncogenic Notch mutations. A similar effect was not observed when germline tumors were induced by manipulation of other regulators; therefore, this FOG-3 tumor-promoting effect is context dependent. We conclude that FOG-3 can either promote or inhibit proliferation in a manner that is sensitive to both genetic context and gene dosage. The discovery of these FOG-3 effects on proliferation has implications for our understanding of

  4. Simulation of Axial Combustion Instability Development and Suppression in Solid Rocket Motors

    Directory of Open Access Journals (Sweden)

    David R. Greatrix

    2009-03-01

    Full Text Available In the design of solid-propellant rocket motors, the ability to understand and predict the expected behaviour of a given motor under unsteady conditions is important. Research towards predicting, quantifying, and ultimately suppressing undesirable strong transient axial combustion instability symptoms necessitates a comprehensive numerical model for internal ballistic simulation under dynamic flow and combustion conditions. An updated numerical model incorporating recent developments in predicting negative and positive erosive burning, and transient, frequency-dependent combustion response, in conjunction with pressure-dependent and acceleration-dependent burning, is applied to the investigation of instability-related behaviour in a small cylindrical-grain motor. Pertinent key factors, like the initial pressure disturbance magnitude and the propellant's net surface heat release, are evaluated with respect to their influence on the production of instability symptoms. Two traditional suppression techniques, axial transitions in grain geometry and inert particle loading, are in turn evaluated with respect to suppressing these axial instability symptoms.

  5. Disposition Kinetics and Optimal Dosage of Ciprofloxacin in Healthy Domestic Ruminant Species

    Directory of Open Access Journals (Sweden)

    Ijaz Javed

    2009-01-01

    Full Text Available The purpose of this experimental study was to determine the disposition kinetics and optimal dosages of ciprofloxacin in healthy domestic ruminant species including adult female buffalo, cow, sheep and goat. The drug was given as a single intramuscular dose of 5 mg/kg. The plasma concentrations of the drug were determined with HPLC and pharmacokinetic variables were determined. The biological half-life (t1/2 β was longer in cows (3.25 ± 0.46 h followed by intermediate values in buffaloes (3.05 ± 0.20 h and sheep (2.93 ± 0.45 h and shorter in goats (2.62 ± 0.39 h. The volume of distribution (Vd in buffaloes was 1.09 ± 0.06 l/kg, cows 1.24 ± 0.16 l/kg, sheep 2.89 ± 0.30 l/kg and goats 3.76 ± 0.92 l/kg. Total body clearance (ClB expressed in l/h/kg was minimum in buffaloes 0.25 ± 0.02 followed by values in cows 0.31 ± 0.02 and sheep 0.75 ± 0.04 and maximum in goats 1.09 ± 0.11. An optimal dosage regimen for 12-h interval consisted of 5.17, 5.62, 6.54 and 6.10 mg/kg body weight as priming and 4.84, 5.37, 6.26 and 5.91 mg/kg body weight as maintenance intramuscular dose in buffalo, cow, sheep and goat, respectively. The manufacturers of ciprofloxacin have claimed 5 mg/kg dose to be repeated after 24 h. However, the investigated dosage regimen may be repeated after 12 h to maintain MIC at the end of the dosage interval. Therefore, it is imperative that an optimal dosage regimen be based on the disposition kinetics data determined in the species and environment in which a drug is to be employed clinically.

  6. ACE-it: a tool for genome-wide integration of gene dosage and RNA expression data

    NARCIS (Netherlands)

    van Wieringen, W.N.; Belien, J.A.M.; Vosse, S.; Achame, E.M.; Ylstra, B.

    2006-01-01

    Summary: We describe a tool, called ACE-it (Array CGH Expression integration tool). ACE-it links the chromosomal position of the gene dosage measured by array CGH to the genes measured by the expression array. ACE-it uses this link to statistically test whether gene dosage affects RNA expression. ©

  7. Miniaturized approach for excipient selection during the development of oral solid dosage form

    DEFF Research Database (Denmark)

    Raijada, Dharaben Kaushikkumar; Müllertz, Anette; Cornett, Claus

    2014-01-01

    The present study introduces a miniaturized high-throughput platform to understand the influence of excipients on the performance of oral solid dosage forms during early drug development. Wet massing of binary mixtures of the model drug (sodium naproxen) and representative excipients was followed...... for excipient selection and for early-stage performance testing of active pharmaceutical ingredient intended for oral solid dosage form. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:900-908, 2014....

  8. Noise-driven diamagnetic susceptibility of impurity doped quantum dots: Role of anisotropy, position-dependent effective mass and position-dependent dielectric screening function

    International Nuclear Information System (INIS)

    Bera, Aindrila; Saha, Surajit; Ganguly, Jayanta; Ghosh, Manas

    2016-01-01

    Highlights: • Diamagnetic susceptibility (DMS) of doped quantum dot is studied. • The dot is subjected to Gaussian white noise. • Role of anisotropy, PDEM and PDDSF have been analyzed. • Noise amplifies and suppresses DMS depending on particular condition. • Findings bear significant technological importance. - Abstract: We explore Diamagnetic susceptibility (DMS) of impurity doped quantum dot (QD) in presence of Gaussian white noise introduced to the system additively and multiplicatively. In view of this profiles of DMS have been pursued with variations of geometrical anisotropy and dopant location. We have invoked position-dependent effective mass (PDEM) and position-dependent dielectric screening function (PDDSF) of the system. Presence of noise sometimes suppresses and sometimes amplifies DMS from that of noise-free condition and the extent of suppression/amplification depends on mode of application of noise. It is important to mention that the said suppression/amplification exhibits subtle dependence on use of PDEM, PDDSF and geometrical anisotropy. The study reveals that DMS, or more fundamentally, the effective confinement of LDSS, can be tuned by appropriate mingling of geometrical anisotropy/effective mass/dielectric constant of the system with noise and also on the pathway of application of latter.

  9. Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae quorum sensing

    DEFF Research Database (Denmark)

    Svenningsen, Sine L; Tu, Kimberly C; Bassler, Bonnie L

    2009-01-01

    the quorum regulatory RNAs 1-4 (Qrr1-4). The four Qrr sRNAs are functionally redundant. That is, expression of any one of them is sufficient for wild-type quorum-sensing behaviour. Here, we show that the combined action of two feedback loops, one involving the sRNA-activator LuxO and one involving the sRNA......Quorum sensing is a mechanism of cell-to-cell communication that allows bacteria to coordinately regulate gene expression in response to changes in cell-population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway reside four homologous small RNAs (sRNAs), named......-target HapR, promotes gene dosage compensation between the four qrr genes. Gene dosage compensation adjusts the total Qrr1-4 sRNA pool and provides the molecular mechanism underlying sRNA redundancy. The dosage compensation mechanism is exquisitely sensitive to small perturbations in Qrr levels. Precisely...

  10. Andrographolide downregulates the v-Src and Bcr-Abl oncoproteins and induces Hsp90 cleavage in the ROS-dependent suppression of cancer malignancy.

    Science.gov (United States)

    Liu, Sheng-Hung; Lin, Chao-Hsiung; Liang, Fong-Ping; Chen, Pei-Fen; Kuo, Cheng-Deng; Alam, Mohd Mujahid; Maiti, Barnali; Hung, Shih-Kai; Chi, Chin-Wen; Sun, Chung-Ming; Fu, Shu-Ling

    2014-01-15

    Andrographolide is a diterpenoid compound isolated from Andrographis paniculata that exhibits anticancer activity. We previously reported that andrographolide suppressed v-Src-mediated cellular transformation by promoting the degradation of Src. In the present study, we demonstrated the involvement of Hsp90 in the andrographolide-mediated inhibition of Src oncogenic activity. Using a proteomics approach, a cleavage fragment of Hsp90α was identified in andrographolide-treated cells. The concentration- and time-dependent induction of Hsp90 cleavage that accompanied the reduction in Src was validated in RK3E cells transformed with either v-Src or a human truncated c-Src variant and treated with andrographolide. In cancer cells, the induction of Hsp90 cleavage by andrographolide and its structural derivatives correlated well with decreased Src levels, the suppression of transformation, and the induction of apoptosis. Moreover, the andrographolide-induced Hsp90 cleavage, Src degradation, inhibition of transformation, and induction of apoptosis were abolished by a ROS inhibitor, N-acetyl-cysteine. Notably, Hsp90 cleavage, decreased levels of Bcr-Abl (another known Hsp90 client protein), and the induction of apoptosis were also observed in human K562 leukemia cells treated with andrographolide or its active derivatives. Together, we demonstrated a novel mechanism by which andrographolide suppressed cancer malignancy that involved inhibiting Hsp90 function and reducing the levels of Hsp90 client proteins. Our results broaden the molecular basis of andrographolide-mediated anticancer activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Multipotent Adult Progenitor Cells Suppress T Cell Activation in In Vivo Models of Homeostatic Proliferation in a Prostaglandin E2-Dependent Manner

    Science.gov (United States)

    Carty, Fiona; Corbett, Jennifer M.; Cunha, João Paulo M. C. M.; Reading, James L.; Tree, Timothy I. M.; Ting, Anthony E.; Stubblefield, Samantha R.; English, Karen

    2018-01-01

    Lymphodepletion strategies are used in the setting of transplantation (including bone marrow, hematopoietic cell, and solid organ) to create space or to prevent allograft rejection and graft versus host disease. Following lymphodepletion, there is an excess of IL-7 available, and T cells that escape depletion respond to this cytokine undergoing accelerated proliferation. Moreover, this environment promotes the skew of T cells to a Th1 pro-inflammatory phenotype. Existing immunosuppressive regimens fail to control this homeostatic proliferative (HP) response, and thus the development of strategies to successfully control HP while sparing T cell reconstitution (providing a functioning immune system) represents a significant unmet need in patients requiring lymphodepletion. Multipotent adult progenitor cells (MAPC®) have the capacity to control T cell proliferation and Th1 cytokine production. Herein, this study shows that MAPC cells suppressed anti-thymocyte globulin-induced cytokine production but spared T cell reconstitution in a pre-clinical model of lymphodepletion. Importantly, MAPC cells administered intraperitoneally were efficacious in suppressing interferon-γ production and in promoting the expansion of regulatory T cells in the lymph nodes. MAPC cells administered intraperitoneally accumulated in the omentum but were not present in the spleen suggesting a role for soluble factors. MAPC cells suppressed lymphopenia-induced cytokine production in a prostaglandin E2-dependent manner. This study suggests that MAPC cell therapy may be useful as a novel strategy to target lymphopenia-induced pathogenic T cell responses in lymphodepleted patients. PMID:29740426

  12. [The most effective dosage in the administration of PGF2-alpha for interruption of pregnancy during the 2d trimester].

    Science.gov (United States)

    Herczeg, J; Szontágh, F

    1974-06-23

    Artificial interruption of pregnancy contains too many risks from the 12th week of pregnancy. The authors have been working at finding the most suitable and effective dosage of prostaglandin for the interruption of pregnancy during the 2nd trimester. The new dosage experimented was 25 mg of prostaglandin F2alpha, followed by another 25 mg 6 hours later. The clinical efficiency of this dosage was tested. This procedures was used in 45 cases. The efficiency of the method was compared to the efficiency of the previously used dosage, which was 25 mg of prostaglandin F2alpha, followed by 25 mg 24 hours later. The new dosage was evaluated 91% efficient, while the previous dosage was found to be 75% efficient. The side effects were rated as acceptable by the patients. There was no case of infection. Two undeniable advantages were found with this new dosage: the duration of the actual procedure is considerably reduced, and the method appears to be much safer. The authors conclude that this new procedure offers numerous clinical advantages.

  13. Study on image quality and dosage comparison of F/S system and DR system

    International Nuclear Information System (INIS)

    Kim, Sun Chil; Jung, Jae Eun

    2003-01-01

    Currently, many hospital are hastening to introduce digital radiography systems. This is a direct result of the intentions to improve medical services and to digitalized radiology information systems, and is also leading to the improvement of medical imaging technology. Throughout F/S system's long history, many people have researched the image quality and dosage concerning these systems, and as a result, huge improvements in the dosage of patients were possible. Similarly, I believe that DR systems need the same kind of effort. Of course, decreases in dosage that ignore image quality are unthinkable. The results of experiments conducted by five hospitals during a period of 3 months brought to us the conclusions listed below. Based on the comparison and analysis of the exposure control of F/S systems and DR systems, DR systems generally showed higher exposure control for parts of the phantom that became thicker, and the exposure control improved rapidly as the thickness increased. DR systems still proved to be somewhat deficient in resolution measurements compared to existing F/S systems. The image processing part of DR systems contributed much to these result. Under conditions used clinically, the dosage measurements of DR systems were generally higher regardless of region. According to the evaluation of image quality, DR systems showed a higher degree of satisfaction as the thickness of the region became thinner. As mentioned above and based on the mutual relationship experiments between the dosage and image quality of F/S systems and DR systems, research to increase the satisfaction of DR systems must be considered

  14. Gonadal dosage during hip dysplasia radiography in the dog.

    Science.gov (United States)

    Wood, A K; Reynolds, K M; Leith, I S; Burns, P A

    1977-01-01

    Thermoluminescent dosemeters were used to estimate gonadal dosage during hip dysplasia radiography of labrador retriever dogs. The mean radiation dose to the unshielded testes was 100 millirad (mrad) and the estimated dose to the shielded testes was 9 mrad. It was considered unnecessary to shield the ovaries.

  15. Gamma ray dosage and mutation breeding in St. Augustinegrass

    International Nuclear Information System (INIS)

    Busey, P.

    1980-01-01

    Stolon pieces of St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze] were irradiated with gamma rays in an attempt to cause mutations. A practical dosage for most genotypes was 4,500 rads. This dosage caused considerable (50%) growth retardation and a mean survival of about 40% of single-node cuttings. However, Bitterblue and another accession were entirely killed at 4,000 rads. At 4,500 rads, up to 7% recognizable mutants of accession FA-243 were obtained. This proportion resulted when irradiated cuttings were propagated clonally and observed for 1.5 years in replicated microplots. In addition to morphological variants, a chimeral anthocyanin change was noticed. From this chimera arose a stable genotype with green stolons and white stigmas, whereas the source genotype (FA-243) had red stolons and purple stigmas. Associated reduction in fertility from 56 to 0.6% suggested that the mutation arose as a small chromosome deletion. Mutation breeding is effective in improving St. Augustinegrass when easily recognizable variants are needed

  16. Absorption of macronutrients by cassava in different harvest dates and dosages of nitrogen

    Directory of Open Access Journals (Sweden)

    Nádia Souza dos Santos

    Full Text Available A field experiment was carried out in 2010-2011 crop years in the experimental area of the Centro de Ciências Agrárias of the Universidade Federal de Roraima, in Boa Vista, Roraima, Brazil. This study aimed to evaluate the effect of nitrogen availability on the concentrations of N, P, K, Ca, Mg and S in cassava, cultivar Aciolina, in different harvest times. A randomized block design was used in split-plot, with four replications. Dosages of N in cover were applied randomly on the plots (0, 30, 60, 150 and 330 kg ha-1, and in the subplot the harvest dates 120, 150, 180, 210, 240, 270 and 300 days after emergence (DAE. The vegetal material was collected, ground and then underwent an analysis for determination of nutrients concentrations in the leaves (N, P, K, Ca Mg and S. The harvest dates and dosages of N affect the nutrient concentrations in the cassava leaves, cv. Aciolina. The macronutrients dosage in the leaves, 120 DAE, is a good indicator of the nutritional status of the cassava plant. The dosage of 150 kg ha-1 of N raises the tubers roots per plant. The sequence of the macronutrients concentration in the leaves of the cassava, cv. Aciolina is N>Ca>K>Mg>P>S.

  17. Optimal Antibiotic Dosage for Chronic Kidney Disease Patient: A Pharmacological Manual for Oral Clinicians.

    Science.gov (United States)

    Chidambaram, Ramasamy

    2015-01-01

    Chronic kidney disease, (CKD) a gradual and inevitable deterioration in renal function, is the disease with the most associations in dentistry. Dosage adjustment is one amongst the vital elements to be familiar with during their oral care. CKD patients take extended duration to filter out medications, therefore dosage must always be tailored under the supervision of nephrologist. The relished benefits from antibiotic could transform as anti-microbial resistance on their abuse and nephrotoxic when contraindicated drugs are encouraged. New patented drug belonging to oxazoliodine group has driven the researchers to handle the emerging AMR. The present communication discusses the pharmacological factors influencing in prescribing the antibiotics for CKD patient from the dentist's point of view. The formulas destined for calculating the optimal dosage of antibiotics have been documented to aid oral physicians.

  18. Characterisation of lung tumour under dosage for interpretation of clinical trial data

    International Nuclear Information System (INIS)

    Taylor, M.L.; Dunn, L.; Franich, R.D.; Kron, T.; Height, F.

    2010-01-01

    Full text: It is well known that the periphery of lung tumours is under-dosed in radiotherapy as a result of electronic disequilibrium at the interface of lung and tumour tissue. Clinical trials often employ dose calculation algorithms which poorly approximate the dose to peripheral regions of tumour volumes. The aim of this study was to develop a set of systematic under-dosage estimates corresponding to various clinical parameters. High resolution Monte Carlo radiation transport calculations were undertaken for a systematic set of generic lung tumours irradiated with an external photon beam. Varied parameters include beam energy, field size, tumour size and distance to chest wall. Calculations were undertaken using both EGSnrc and GEAI T4. A 'Dose Reduction Factor' is defined which describes the dose to the peripheral 'shell' 01 the tumour, as relevant for multiple-field and arc therapy. For a 6 MV beam, under-dosage is typically between 2 and 5% for the different arrangements investigated, and for a 15 MV beam it is between 5 and 8% (relative to the central dose). Good agreement between EGSnrc and GEANT4 was demonstrated. Comparisons with pencil beam convolution calculations indicate that the treatment planning system does not identify this under-dosage. A systematic set of data has been obtained that characterises the extent of peripheral under-dosage in lung tumours for the retrospective evaluation of clinical trial data. The data presented i: also informative for clinics using less sophisticated planning algorithms, particularly when dose is being prescribed to covering isodoses. (author)

  19. Influence of Postprandial Intragastric Pressures on Drug Release from Gastroretentive Dosage Forms.

    Science.gov (United States)

    Schneider, Felix; Hoppe, Melanie; Koziolek, Mirko; Weitschies, Werner

    2018-05-29

    Despite extensive research in the field of gastroretentive dosage forms, this "holy grail" of oral drug delivery yet remained an unmet goal. Especially under fasting conditions, the reproducible retention of dosage forms in the stomach seems to be an impossible task. This is why such systems are often advised to be taken together with food. But also the postprandial motility can contribute significantly to the failure of gastroretentive dosage forms. To investigate the influence of postprandial pressure conditions on drug release from such systems, we used a novel in vitro dissolution tool, the dissolution stress test device. With the aid of this device, we simulated three different intragastric pressure profiles that may occur after postprandial intake. These transit scenarios were based on recently obtained, postprandial SmartPill® data. The tested systems, Glumetza® 1000 and Madopar® HBS 125, are marketed dosage forms that are based on different approaches to achieve proper gastric retention. All three transit scenarios revealed a highly pressure-sensitive drug release behavior, for both drugs. For Madopar® HBS 125, nearly complete drug release was observed even after early occurring pressures. Glumetza® 1000 seemed to be more resistant to these, most likely due to incomplete wetting of the system. On the contrary to these findings, data from standard dissolution tests using the paddle apparatus displayed controlled drug release for both systems for about 6 h. Based on these results, it can be doubted that established gastroretentive systems stay intact over a longer period of time, even under postprandial conditions.

  20. Methadone dosage and its relationship to quality of life, satisfaction, psychopathology, cognitive performance and additional consumption of non-prescribed drugs.

    Science.gov (United States)

    Pedrero-Pérez, Eduardo J; MethaQoL, Grupo

    2016-06-14

    The effectiveness of methadone maintenance treatment is beyond any doubt, but there remains some incertitude about the appropriate and effective dosage and the objectives that should be achieved by this therapy. Some authors maintain that only doses higher than 50-60 mg/day ought to be considered effective, since only these block all the opioid receptors. But others propose the use of doses adjusted to the needs of the patient, based on their recovery process. Quality of life, satisfaction with treatment, psychopathological symptoms, cognitive performance and additional intake of illegal and unprescribed drugs were evaluated in a representative sample of all patients treated with opioid agonists in the Addiction Institute of Madrid (N = 1898, n = 450) and the Junta de Extremadura (N = 100, n = 65). The results revealed a negative relationship between dose and quality of life, psychopathological symptoms and cognitive performance. Satisfaction with treatment, based on doses negotiated together by doctor and patient, was very high, regardless of the dose. To establish hypothetical causal dependencies among the studied variables structural equation modelling was performed. The results reject the need for high dosage if not required by the patient, and highlight the benefits of other psychosocial interventions that lead to recovery, despite the chronification that could imply the use of high doses. Whereas high dosage programmes provide better indicators of social control, the patient's quality of life must be one of the main indicators of a successful treatment, as in any other health problem.

  1. Biowaiver monographs for immediate release solid oral dosage forms: piroxicam.

    Science.gov (United States)

    Shohin, Igor E; Kulinich, Julia I; Ramenskaya, Galina V; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Groot, D W; Barends, Dirk M; Dressman, Jennifer B

    2014-02-01

    Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo. © 2013 Wiley Periodicals, Inc. and the

  2. Formulation and evaluation of tablet dosage form of Hunteria ...

    African Journals Online (AJOL)

    The present study was aimed at formulating and evaluating tablet dosage form of Hunteria umbellata (HU) seed aqueous and purified extracts. HU seeds were dried, pulverized and the powder macerated in water to obtain aqueous extract, while alkaloidal extraction process was used to obtain purified extract. Extracts ...

  3. Dropwise additive manufacturing of pharmaceutical products for solvent-based dosage forms.

    Science.gov (United States)

    Hirshfield, Laura; Giridhar, Arun; Taylor, Lynne S; Harris, Michael T; Reklaitis, Gintaras V

    2014-02-01

    In recent years, the US Food and Drug Administration has encouraged pharmaceutical companies to develop more innovative and efficient manufacturing methods with improved online monitoring and control. Mini-manufacturing of medicine is one such method enabling the creation of individualized product forms for each patient. This work presents dropwise additive manufacturing of pharmaceutical products (DAMPP), an automated, controlled mini-manufacturing method that deposits active pharmaceutical ingredients (APIs) directly onto edible substrates using drop-on-demand (DoD) inkjet printing technology. The use of DoD technology allows for precise control over the material properties, drug solid state form, drop size, and drop dynamics and can be beneficial in the creation of high-potency drug forms, combination drugs with multiple APIs or individualized medicine products tailored to a specific patient. In this work, DAMPP was used to create dosage forms from solvent-based formulations consisting of API, polymer, and solvent carrier. The forms were then analyzed to determine the reproducibility of creating an on-target dosage form, the morphology of the API of the final form and the dissolution behavior of the drug over time. DAMPP is found to be a viable alternative to traditional mass-manufacturing methods for solvent-based oral dosage forms. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. Ah receptor mediated suppression of the antibody response in mice is primarily dependent on the Ah phenotype of lymphoid tissue

    International Nuclear Information System (INIS)

    Silkworth, J.B.; Antrim, L.A.; Sack, G.

    1986-01-01

    Halogenated aromatic hydrocarbons act through the aromatic hydrocarbon (Ah) receptor in mice to produce a series of toxic effects of the immune system. The receptor protein is a product of the Ah gene locus. Ah responsive (Ahb/Ahb) mice express a high affinity receptor in both lymphoid and nonlymphoid tissues whereas nonresponsive Ahd/Ahd mice express a poor affinity receptor. To determine the role of the Ah receptor of lymphoid tissue relative to that of nonlymphoid tissue in the induction of immune impairment, bone marrow was used to reconstitute lethally irradiated mice of the same or opposite Ah phenotype. All mice were given 3,3',4,4'-tetrachlorobiphenyl (35 and 350 mumol/kg) ip 2 days before immunization with sheep erythrocytes (SRBC). The immune response to this T dependent antigen and organ weights were determined 5 or 7 days later in normal or chimeric mice, respectively. Monoclonal Lyt 1.1 and Lyt 1.2 antibodies were used to establish the origin of the cells which repopulated the chimeric thymuses. The immune responses of both BALB/cBy (Ahb/Ahb) and the BALB/cBy X DBA/2 hybrid, CByD2F1 (Ahb/Ahd), were significantly suppressed but DBA/2 mice were unaffected. The immune responses of chimeric BALB/cBy----BALB/cBy and BALB/cBy----DBA/2 (donor----recipient) mice were also significantly suppressed and thymic atrophy was observed in both cases. The serum anti-SRBC antibody titers of DBA/2----BALB/cBy chimeras were also significantly decreased although not to the same extent as in BALB/cBy----DBA/2 mice. Chimeric DBA/2----DBA/2 mice were not affected. These results indicate that the sensitivity to Ah receptor mediated suppression of the antibody response is primarily determined by the Ah phenotype of the lymphoid tissue

  5. [Autologous regulatory T cells can suppress the proliferation of lymphoma cell line in vitro].

    Science.gov (United States)

    Ying, Zhi-Tao; Guo, Jun; Ren, Jun; Kong, Yan; Yuan, Zhi-Hong; Liu, Xi-Juan; Zhang, Chen; Zheng, Wen; Song, Yu-Qin; Zhang, Yun-Tao; Zhu, Jun

    2009-06-01

    This study was aimed to investigate the suppressive effect of regulatory T (Treg) cells on the T cell lymphoma EL4 cell line and to explore its mechanism. C57BL/6 Mouse Treg cells were isolated by MACS (magnetic cell sorting). The purity and the expression of Foxp3 were detected by flow cytometry. The suppressive effect of sorted Treg cells on EL4 cells was detected by MTT assay. The secretion of TGF-beta1 and IL-10 was examined by enzyme-linked immunosorbent assay (ELISA). The results showed that CD4(+)CD25(+) T cells could be successfully isolated by MACS with the purity reaching 91.6% and the expression level of Foxp3 was 78.9%. The ratio of viable cells was more than 95%. Regulatory T cells could suppress the proliferation of EL4 cells effectively in the presence of antigen presenting cells (APCs). And the suppressive effect was most significant at 1:1 ratio. In addition, the suppression still existed without APCs. TGF-beta1 and IL-10 could not be detected by ELISA. It is concluded that the Treg cells can suppress T lymphoma cell in vitro. The suppressive effect of Treg cells works in dose-dependent manner, but not in cytokine-dependent manner. The mechanism of this suppression may take effect through cell-cell contact.

  6. T1 pseudohyperintensity on fat-suppressed MRI: A potential diagnostic pitfall

    Science.gov (United States)

    Huynh, Tuan N.; Johnson, D. Thor; Poder, Liina; Joe, Bonnie N.; Webb, Emily M.; Coakley, Fergus V.

    2011-01-01

    MRI findings in two patients with misleading T1 hyperintensity seen only on fat-suppressed images are presented, one with a renal cell carcinoma that was misinterpreted as a hemorrhagic cyst and the other with an ovarian serous cystadenocarcinoma that was misinterpreted as a complicated endometrioma. The apparent T1 hyperintensity on fat suppressed images in these cases was likely due to varying perception of image signal dependent on local contrast, an optical effect known as the checker-shadow illusion. T1 pseudohyperintensity should be considered when apparently high T1 signal intensity is seen only on fat-suppressed images; review of non fat-suppressed images may help prevent an erroneous diagnoses of blood-containing lesions. PMID:21765301

  7. Peripheral Inhibitor of AChE, Neostigmine, Prevents the Inflammatory Dependent Suppression of GnRH/LH Secretion during the Follicular Phase of the Estrous Cycle

    Directory of Open Access Journals (Sweden)

    Andrzej P. Herman

    2017-01-01

    Full Text Available The study was designed to test the hypothesis that the inhibition of acetylcholinesterase (AChE activity at the periphery by Neostigmine (0.5 mg/animal will be sufficient to prevent inflammatory dependent suppression of the gonadotropin-releasing hormone (GnRH/luteinising hormone (LH secretion in ewes in the follicular phase of the estrous cycle, and this effect will be comparable with the systemic AChE inhibitor, Donepezil (2.5 mg/animal. An immune/inflammatory challenge was induced by peripheral administration of lipopolysaccharide (LPS; 400 ng/kg. Peripheral treatment with Donepezil and Neostigmine prevented the LPS-induced decrease (P<0.05 in LHβ gene expression in the anterior pituitary gland (AP and in LH release. Moreover, Donepezil completely abolished (P<0.05 the suppressory effect of inflammation on GnRH synthesis in the preoptic area, when pretreatment with Neostigmine reduced (P<0.05 the decrease in GnRH content in this hypothalamic structure. Moreover, administration of both AChE inhibitors diminished (P<0.05 the inhibitory effect of LPS treatment on the expression of GnRH receptor in the AP. Our study shows that inflammatory dependent changes in the GnRH/LH secretion may be eliminated or reduced by AChE inhibitors suppressing inflammatory reaction only at the periphery such as Neostigmine, without the need for interfering in the central nervous system.

  8. Identification and analcime quantification; Identification et dosage de l'analcime

    Energy Technology Data Exchange (ETDEWEB)

    Chantret, F; Guillemaut, A; Pouget, R

    1962-07-01

    The authors are comparing thermal analysis and X-ray diffraction methods for the estimation of analcime in rocks. From application to the analcimolithes of Agades - Republic of Niger - it appears that X-ray diffractometry is better convenient, both for identification and estimation; nevertheless, thermal analysis combined with chemical analysis allows to detect variations in the composition of analcime inside a given series. [French] Les auteurs comparent les techniques d'analyse thermique et de diffraction X pour le dosage de l'analcime dans les roches. L'application aux analcimolites d'Agades - Republique du Niger - montre que la diffractometrie X est mieux adaptee a la fois dans l'identification et le dosage; neanmoins, l'analyse thermique, associee a l'analyse chimique, permet de suivre les fluctuations de composition de l'analcime a l'interieur d'une serie determinee. (auteurs)

  9. Fuzzy-based dosage model of aqueous decoction of Adansonia ...

    African Journals Online (AJOL)

    However, in the area of traditional medicine, no much attention has been given to its enhancement with the use of information technology especially in the area of herbal prescription. ... The mass of herb and volume of solvent were used as input parameters to design the dosage model, and simulated using MATLAB.

  10. Attenuation of Morphine Withdrawal Syndrome by Various Dosages of Curcumin in Comparison with Clonidine in Mouse: Possible Mechanism

    Directory of Open Access Journals (Sweden)

    Majid Motaghinejad

    2015-03-01

    Full Text Available Background: Herbal medical compounds and their major constituent have been used in the management and treatment of opioid withdrawal syndrome and pain. This study was carried out to clarify the effect of curcumin, the major compound of turmeric, on morphine withdrawal syndrome in mouse model and its possible mechanisms of pain relieving activity by assessing in writhing test as a model of visceral pain. Methods: Due to two separate protocols (withdrawal syndrome and pain, 144 male albino mice were divided in two major groups. In withdrawal syndrome group, test effect of various dosages of curcumin (10, 20, and 40 mg/kg was assessed on withdrawal signs and compared with positive and negative control and standard treatment (clonidine 0.4 mg/kg groups. In pain groups, to determine the mechanism of pain relieving activity of curcumin, various dosages of curcumin (10, 20, and 40 mg/kg in three separated groups, were used against acetic acid induced writhing (which is a constriction test. The most effective dose (40 mg/kg was used in writhing test and compared with groups pretreated with antagonist of major neurotransmitters involved in pain; and compared with group pretreated with vehicle (DMSO, 0.05% as control. Results: Curcumin attenuates withdrawal syndrome in a dose dependent manner in comparison with the dependent positive control group (P<0.05. It also indicated that pretreatment with naloxone and cyproheptadine significantly attenuate antinociception effect of curcumin (P<0.05. Conclusion: This study advocate that antinociception of curcumin was mediated by opioidergic and adrenergic system.

  11. Curcumin Triggers p16-Dependent Senescence in Active Breast Cancer-Associated Fibroblasts and Suppresses Their Paracrine Procarcinogenic Effects

    Directory of Open Access Journals (Sweden)

    Siti-Fauziah Hendrayani

    2013-06-01

    Full Text Available Activated cancer-associated fibroblasts (CAFs or myofibroblasts not only facilitate tumor growth and spread but also affect tumor response to therapeutic agents. Therefore, it became clear that efficient therapeutic regimens should also take into account the presence of these supportive cells and inhibit their paracrine effects. To this end, we tested the effect of low concentrations of curcumin, a pharmacologically safe natural product, on patient-derived primary breast CAF cells. We have shown that curcumin treatment upregulates p16INK4A and other tumor suppressor proteins while inactivates the JAK2/STAT3 pathway. This reduced the level of alpha-smooth muscle actin (α-SMA and the migration/invasion abilities of these cells. Furthermore, curcumin suppressed the expression/secretion of stromal cell-derived factor-1 (SDF-1, interleukin-6 (IL-6, matrix metalloproteinase-2 (MMP-2, MMP-9, and transforming growth factor-β, which impeded their paracrine procarcinogenic potential. Intriguingly, these effects were sustained even after curcumin withdrawal and cell splitting. Therefore, using different markers of senescence [senescence-associated β-galactosidase (SA-β-gal activity, Ki-67 and Lamin B1 levels, and bromodeoxyuridine incorporation], we have shown that curcumin markedly suppresses Lamin B1 and triggers DNA damage-independent senescence in proliferating but not quiescent breast stromal fibroblasts. Importantly, this curcumin-related senescence was p16INK4A-dependent and occurred with no associated inflammatory secretory phenotype. These results indicate the possible inactivation of cancer-associated myofibroblasts and present the first indication that curcumin can trigger DNA damage-independent and safe senescence in stromal fibroblasts.

  12. The effect of decreasing computed tomography dosage on radiostereometric analysis (RSA) accuracy at the glenohumeral joint.

    Science.gov (United States)

    Fox, Anne-Marie V; Kedgley, Angela E; Lalone, Emily A; Johnson, James A; Athwal, George S; Jenkyn, Thomas R

    2011-11-10

    Standard, beaded radiostereometric analysis (RSA) and markerless RSA often use computed tomography (CT) scans to create three-dimensional (3D) bone models. However, ethical concerns exist due to risks associated with CT radiation exposure. Therefore, the aim of this study was to investigate the effect of decreasing CT dosage on RSA accuracy. Four cadaveric shoulder specimens were scanned using a normal-dose CT protocol and two low-dose protocols, where the dosage was decreased by 89% and 98%. 3D computer models of the humerus and scapula were created using each CT protocol. Bi-planar fluoroscopy was used to image five different static glenohumeral positions and two dynamic glenohumeral movements, of which a total of five static and four dynamic poses were selected for analysis. For standard RSA, negligible differences were found in bead (0.21±0.31mm) and bony landmark (2.31±1.90mm) locations when the CT dosage was decreased by 98% (p-values>0.167). For markerless RSA kinematic results, excellent agreement was found between the normal-dose and lowest-dose protocol, with all Spearman rank correlation coefficients greater than 0.95. Average root mean squared errors of 1.04±0.68mm and 2.42±0.81° were also found at this reduced dosage for static positions. In summary, CT dosage can be markedly reduced when performing shoulder RSA to minimize the risks of radiation exposure. Standard RSA accuracy was negligibly affected by the 98% CT dose reduction and for markerless RSA, the benefits of decreasing CT dosage to the subject outweigh the introduced errors. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.

    Directory of Open Access Journals (Sweden)

    Erica Larschan

    Full Text Available Sex chromosome dosage compensation in Drosophila provides a model for understanding how chromatin organization can modulate coordinate gene regulation. Male Drosophila increase the transcript levels of genes on the single male X approximately two-fold to equal the gene expression in females, which have two X-chromosomes. Dosage compensation is mediated by the Male-Specific Lethal (MSL histone acetyltransferase complex. Five core components of the MSL complex were identified by genetic screens for genes that are specifically required for male viability and are dispensable for females. However, because dosage compensation must interface with the general transcriptional machinery, it is likely that identifying additional regulators that are not strictly male-specific will be key to understanding the process at a mechanistic level. Such regulators would not have been recovered from previous male-specific lethal screening strategies. Therefore, we have performed a cell culture-based, genome-wide RNAi screen to search for factors required for MSL targeting or function. Here we focus on the discovery of proteins that function to promote MSL complex recruitment to "chromatin entry sites," which are proposed to be the initial sites of MSL targeting. We find that components of the NSL (Non-specific lethal complex, and a previously unstudied zinc-finger protein, facilitate MSL targeting and display a striking enrichment at MSL entry sites. Identification of these factors provides new insight into how MSL complex establishes the specialized hyperactive chromatin required for dosage compensation in Drosophila.

  14. Determination of the Minimum Effective Dosages of Praziquantel, Albendazole, and Mebendazole Against Clonorchis Sinensis Infection in Rats

    Directory of Open Access Journals (Sweden)

    Ping-Chin Fan

    2005-10-01

    Full Text Available In order to determine the minimum effective dosages of praziquantel, albendazole, and mebendazole against Clonorchis sinensis infection in Sprague-Dawley rats, each rat was infected with 30 metacercariae and treated with one of three drugs. The rats were killed and examined 25 days after praziquantel treatment or 11 days after albendazole or mebendazole treatment. The minimum effective dosages were a single dose of praziquantel 375 mg/kg, albendazole 150 mg/kg, and mebendazole 150 mg/kg. Trials are required to determine whether these dosages are useful in the treatment of human clonorchiasis.

  15. Dose-dependent suppression by ethanol of transient auditory 40-Hz response.

    Science.gov (United States)

    Jääskeläinen, I P; Hirvonen, J; Saher, M; Pekkonen, E; Sillanaukee, P; Näätänen, R; Tiitinen, H

    2000-02-01

    Acute alcohol (ethanol) challenge is known to induce various cognitive disturbances, yet the neural basis of the effect is poorly known. The auditory transient evoked gamma-band (40-Hz) oscillatory responses have been suggested to be associated with various perceptual and cognitive functions in humans; however, alcohol effects on auditory 40-Hz responses have not been investigated to date. The objective of the study was to test the dose-related impact of alcohol on auditory transient evoked 40-Hz responses during a selective-attention task. Ten healthy social drinkers ingested, in four separate sessions, 0.00, 0. 25, 0.50, or 0.75 g/kg of 10% (v/v) alcohol solution. The order of the sessions was randomized and a double-blind procedure was employed. During a selective attention task, 300-Hz standard and 330-Hz deviant tones were presented to the left ear, and 1000-Hz standards and 1100-Hz deviants to the right ear of the subjects (P=0. 425 for each standard, P=0.075 for each deviant). The subjects attended to a designated ear, and were to detect the deviants therein while ignoring tones to the other ear. The auditory transient evoked 40-Hz responses elicited by both the attended and unattended standard tones were significantly suppressed by the 0.50 and 0.75 g/kg alcohol doses. Alcohol suppresses auditory transient evoked 40-Hz oscillations already with moderate blood alcohol concentrations. Given the putative role of gamma-band oscillations in cognition, this finding could be associated with certain alcohol-induced cognitive deficits.

  16. Attention Determines Contextual Enhancement versus Suppression in Human Primary Visual Cortex.

    Science.gov (United States)

    Flevaris, Anastasia V; Murray, Scott O

    2015-09-02

    Neural responses in primary visual cortex (V1) depend on stimulus context in seemingly complex ways. For example, responses to an oriented stimulus can be suppressed when it is flanked by iso-oriented versus orthogonally oriented stimuli but can also be enhanced when attention is directed to iso-oriented versus orthogonal flanking stimuli. Thus the exact same contextual stimulus arrangement can have completely opposite effects on neural responses-in some cases leading to orientation-tuned suppression and in other cases leading to orientation-tuned enhancement. Here we show that stimulus-based suppression and enhancement of fMRI responses in humans depends on small changes in the focus of attention and can be explained by a model that combines feature-based attention with response normalization. Neurons in the primary visual cortex (V1) respond to stimuli within a restricted portion of the visual field, termed their "receptive field." However, neuronal responses can also be influenced by stimuli that surround a receptive field, although the nature of these contextual interactions and underlying neural mechanisms are debated. Here we show that the response in V1 to a stimulus in the same context can either be suppressed or enhanced depending on the focus of attention. We are able to explain the results using a simple computational model that combines two well established properties of visual cortical responses: response normalization and feature-based enhancement. Copyright © 2015 the authors 0270-6474/15/3512273-08$15.00/0.

  17. Neural correlate of resting-state functional connectivity under α2 adrenergic receptor agonist, medetomidine.

    Science.gov (United States)

    Nasrallah, Fatima A; Lew, Si Kang; Low, Amanda Si-Min; Chuang, Kai-Hsiang

    2014-01-01

    Correlative fluctuations in functional MRI (fMRI) signals across the brain at rest have been taken as a measure of functional connectivity, but the neural basis of this resting-state MRI (rsMRI) signal is not clear. Previously, we found that the α2 adrenergic agonist, medetomidine, suppressed the rsMRI correlation dose-dependently but not the stimulus evoked activation. To understand the underlying electrophysiology and neurovascular coupling, which might be altered due to the vasoconstrictive nature of medetomidine, somatosensory evoked potential (SEP) and resting electroencephalography (EEG) were measured and correlated with corresponding BOLD signals in rat brains under three dosages of medetomidine. The SEP elicited by electrical stimulation to both forepaws was unchanged regardless of medetomidine dosage, which was consistent with the BOLD activation. Identical relationship between the SEP and BOLD signal under different medetomidine dosages indicates that the neurovascular coupling was not affected. Under resting state, EEG power was the same but a depression of inter-hemispheric EEG coherence in the gamma band was observed at higher medetomidine dosage. Different from medetomidine, both resting EEG power and BOLD power and coherence were significantly suppressed with increased isoflurane level. Such reduction was likely due to suppressed neural activity as shown by diminished SEP and BOLD activation under isoflurane, suggesting different mechanisms of losing synchrony at resting-state. Even though, similarity between electrophysiology and BOLD under stimulation and resting-state implicates a tight neurovascular coupling in both medetomidine and isoflurane. Our results confirm that medetomidine does not suppress neural activity but dissociates connectivity in the somatosensory cortex. The differential effect of medetomidine and its receptor specific action supports the neuronal origin of functional connectivity and implicates the mechanism of its sedative

  18. DAX1 suppresses FXR transactivity as a novel co-repressor

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jin; Lu, Yan; Liu, Ruya; Xiong, Xuelian; Zhang, Zhijian; Zhang, Xianfeng [Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025 (China); Ning, Guang, E-mail: guangning@gmail.com.cn [Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025 (China); The Key Laboratory of Endocrine Tumors and The Division of Endocrine and Metabolic Diseases, E-Institute of Shanghai Universities, Shanghai 200025 (China); Li, Xiaoying, E-mail: lixy@sibs.ac.cn [Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025 (China); The Key Laboratory of Endocrine Tumors and The Division of Endocrine and Metabolic Diseases, E-Institute of Shanghai Universities, Shanghai 200025 (China)

    2011-09-09

    Highlights: {yields} DAX1 is co-localized with FXR and interacts with FXR. {yields} DAX1 acts as a negative regulator of FXR. {yields} Three LXXLL motifs in the N-terminus of DAX1 were required. {yields} DAX1 suppresses FXR transactivation by competing with co-activators. -- Abstract: Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile acid, glucose and lipid homeostasis through regulation of numerous genes involved in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains and acts primarily as a co-repressor of many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR in the nucleus and acted as a negative regulator of FXR through a physical interaction with FXR. Our study showed that over-expression of DAX1 down-regulated the expression of FXR target genes, whereas knockdown of DAX1 led to their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1 were required for the full repression of FXR transactivation. In addition, our study characterized that DAX1 suppresses FXR transactivation via competing with co-activators such as SRC-1 and PGC-1{alpha}. In conclusion, DAX1 acts as a co-repressor to negatively modulate FXR transactivity.

  19. DAX1 suppresses FXR transactivity as a novel co-repressor

    International Nuclear Information System (INIS)

    Li, Jin; Lu, Yan; Liu, Ruya; Xiong, Xuelian; Zhang, Zhijian; Zhang, Xianfeng; Ning, Guang; Li, Xiaoying

    2011-01-01

    Highlights: → DAX1 is co-localized with FXR and interacts with FXR. → DAX1 acts as a negative regulator of FXR. → Three LXXLL motifs in the N-terminus of DAX1 were required. → DAX1 suppresses FXR transactivation by competing with co-activators. -- Abstract: Bile acid receptor FXR (farnesoid X receptor) is a key regulator of hepatic bile acid, glucose and lipid homeostasis through regulation of numerous genes involved in the process of bile acid, triglyceride and glucose metabolism. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains and acts primarily as a co-repressor of many nuclear receptors. Here, we demonstrated that DAX1 is co-localized with FXR in the nucleus and acted as a negative regulator of FXR through a physical interaction with FXR. Our study showed that over-expression of DAX1 down-regulated the expression of FXR target genes, whereas knockdown of DAX1 led to their up-regulation. Furthermore, three LXXLL motifs in the N-terminus of DAX1 were required for the full repression of FXR transactivation. In addition, our study characterized that DAX1 suppresses FXR transactivation via competing with co-activators such as SRC-1 and PGC-1α. In conclusion, DAX1 acts as a co-repressor to negatively modulate FXR transactivity.

  20. Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

    Science.gov (United States)

    Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

    2016-08-23

    Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

  1. Phospholipase C-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate underlies agmatine-induced suppression of N-type Ca2+ channel in rat celiac ganglion neurons.

    Science.gov (United States)

    Kim, Young-Hwan; Jeong, Ji-Hyun; Ahn, Duck-Sun; Chung, Seungsoo

    2017-03-04

    Agmatine suppresses peripheral sympathetic tone by modulating Cav2.2 channels in peripheral sympathetic neurons. However, the detailed cellular signaling mechanism underlying the agmatine-induced Cav2.2 inhibition remains unclear. Therefore, in the present study, we investigated the electrophysiological mechanism for the agmatine-induced inhibition of Cav2.2 current (I Cav2.2 ) in rat celiac ganglion (CG) neurons. Consistent with previous reports, agmatine inhibited I Cav2.2 in a VI manner. The agmatine-induced inhibition of the I Cav2.2 current was also almost completely hindered by the blockade of the imidazoline I 2 receptor (IR 2 ), and an IR 2 agonist mimicked the inhibitory effect of agmatine on I Cav2.2 , implying involvement of IR 2 . The agmatine-induced I Cav2.2 inhibition was significantly hampered by the blockade of G protein or phospholipase C (PLC), but not by the pretreatment with pertussis toxin. In addition, diC8-phosphatidylinositol 4,5-bisphosphate (PIP 2 ) dialysis nearly completely hampered agmatine-induced inhibition, which became irreversible when PIP 2 resynthesis was blocked. These results suggest that in rat peripheral sympathetic neurons, agmatine-induced IR 2 activation suppresses Cav2.2 channel voltage-independently, and that the PLC-dependent PIP 2 hydrolysis is responsible for the agmatine-induced suppression of the Cav2.2 channel. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Dosage of fission products in irradiated fuel treatment effluents (radio-chemical method); Dosage des produits de fission dans les effluents du traitement des combustibles irradies (methode radiochimique)

    Energy Technology Data Exchange (ETDEWEB)

    Auchapt, J [Commissariat a l' Energie Atomique, Marcoule (France). Centre d' Etudes Nucleaires

    1966-07-01

    The dosage methods presented here are applicable to relatively long-lived fission products present in the effluents resulting from irradiated fuel treatment processes (Sr - Cs - Ce - Zr - Nb - Ru - I). The methods are based on the same principle: - addition of a carrying-over agent - chemical separation over several purification stages, - determination of the chemical yield by calorimetry - counting of an aliquot liquid portion. (author) [French] Les methodes de dosage presentees concernent les produits de fission a vie relativement longue presents dans les effluents de traitement des combustibles irradies (Sr - Cs - Ce - Zr - Nb - Ru - I). Elles sont toutes basees sur le meme principe: - addition d'entraineur, - separation chimique en plusieurs stades de purification, - determination du rendement chimique par calorimetrie, - comptage d'une aliquote liquide. (auteur)

  3. Is a serotonergic mechanism involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced appetite suppression in the Sprague-Dawley rat

    Energy Technology Data Exchange (ETDEWEB)

    Rozman, K. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics Gesellschaft fuer Strahlen- und Umweltforschung mbH Muenchen (GSF), Neuherberg (Germany, F.R.). Inst. fuer Toxikologie); Pfeifer, B.; Kerecsen, L.; Alper, R.H. (Kansas Univ., Kansas City, KS (USA). Dept. of Pharmacology, Toxicology and Therapeutics)

    1991-02-01

    The major cause of TCDD-induced death in rats is a progressive voluntary feed refusal which has been correlated with reduced gluconeogenesis. Since centrally administered TCDD does not cause death or decreased feed intake in rats, the ability of TCDD to suppress appetite via peripheral mechanisms acting on the central nervous system was examined in two experimental models. First, it was found that the feed intake of rats on scheduled feeding cycles was not decreased by blood transfused from rats with TCDD-induced appetite suppression (8 days after a lethal dose of TCDD, i.p.). In contrast, a similar transfusion from normal, satiated rats did reduce feed intake of recipient rats by approximately 40%, suggesting that TCDD-treated rats are not satiated but rather that they are not hunggy. In the second study tryptophan (the amino acid precursor of the neutrotransmitter serotonin) was measured in the plasma and tryptophan, serotonin, norepinephrine and dopamine in the hypothalamus as well as dopamine and its metabolites in the striatum 4, 8, and 16 days after TCDD dosage (125 {mu}g/kg, i.p.). Progressive time-dependent increases in tryptophan levels in plasma and brain were paralleled by increases in brain serotonin and 5-hydroxyindoleacetic acid (the primary metabolite of serotonin) in TCDD-treated rats. No changes were observed regarding the other biogenic amines. It is suggested based on these data and on substantial evidence from the published literature that a serotonergic mechanism may be involved in TCDD-induced feed intake reduction. (orig.).

  4. Biowaiver monographs for immediate release solid oral dosage forms: cimetidine.

    NARCIS (Netherlands)

    Jantratid, E; Prakongpan, S; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Barends, D M

    2006-01-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned

  5. Determination of methadone hydrochloride in a maintenance dosage formulation.

    Science.gov (United States)

    Hoffmann, T J; Thompson, R D

    1975-07-01

    A colorimetric method for direct quantitative assay of methadone hydrochloride in liquid oral dosage forms is presented. The procedure involves the formation of a dye complex with bromothymol blue buffer solution. The resultant complex is extracted with benzene and measured spectrophotometrically. Duplicate tests on the formulation showed 99.2% of the labeled amount of methadone.

  6. Formulation of Croton penduliflorus seed into tablet dosage form ...

    African Journals Online (AJOL)

    Formulation of Croton penduliflorus seed into tablet dosage form. GC Onunkwo. Abstract. No Abstract. Global Journal of Medical Sciences Vol. 5(1) 2006: 29-33. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/gjms.v5i1.10145.

  7. In situ experimental study for the optimization of chlorine dosage in seawater cooling systems

    Energy Technology Data Exchange (ETDEWEB)

    Nebot, E.; Casanueva, T.; Fernandez-Baston, M.M.; Sales, D. [Department of Chemical Engineering, Food Technology and Environmental Technologies, University of Cadiz (Spain); Casanueva, J.F. [Department of Thermal Engines, University of Cadiz (Spain)

    2006-11-15

    The paper details an in situ study for the evaluation of the evolution of fouling heat transfer resistance and to optimize the antifouling chlorine dosage at a 550MW power station. A portable pilot plant has been designed to simulate the steam surface condenser and used as an accurate fouling monitor that takes the seawater from the same intake point as the power station. This study includes fouling extraction and its characterization for different dosage patterns. The residual chlorine concentration at the cooling-water discharge from the power station is 0.2mg/l and has been considered appropriate for the prevention of the formation of fouling, because with this concentration approximately 90% reduction in the amount of fouling is obtained. Residual chlorine dosages lower than 0.2ppm could be effective in controlling fouling development if mechanical techniques of fouling control are also available. (author)

  8. Unilateral brief-pulse electroconvulsive therapy and cognition: Effects of electrode placement, stimulus dosage and time.

    LENUS (Irish Health Repository)

    Semkovska, Maria

    2010-11-23

    To clarify advantages of unilateral electrode placement as an optimisation technique for electroconvulsive therapy (ECT) for depression, aims were to meta-analyse unilateral ECT effects on cognitive performance relative to: (1) bitemporal electrode placement, (2) electrical dosage, and (3) time interval between final treatment and cognitive reassessment. Relevant electronic databases were systematically searched through May 2009, using the terms: "electroconvulsive therapy" and ["cogniti∗", "neuropsycholog∗", "memory", "attention", "executive", "spatial", or "intellectual"]. Inclusion criteria were: independent study of depressed patients receiving unilateral or bitemporal brief-pulse ECT; within-subjects design; use of objective cognitive assessments; available mean electrical dosage for unilateral samples. Standardized pre-post ECT weighted effect sizes were computed and pooled within 16 cognitive domains by a mixed-effects model. Thirty-nine studies (1415 patients) were meta-analysed. Up to three days after final treatment, unilateral ECT was associated with significantly smaller decreases in global cognition, delayed verbal memory retrieval, and autobiographical memory, compared to bitemporal ECT. Significant publication bias was found for autobiographical memory, favouring reporting of larger percentage loss. Higher unilateral ECT electrical dosage predicted larger decreases in verbal learning, delayed verbal memory retrieval, visual recognition, and semantic memory retrieval. When retested more than three days after completing ECT, no significant differences remained between the two electrode placements; for unilateral ECT, electrical dosage no longer predicted cognitive performance whereas increasing interval between final treatment and retesting predicted growing improvement in some variables. This interval is a more useful long-term predictor of cognitive function than electrode placement or electrical dosage following unilateral ECT.

  9. Unilateral brief-pulse electroconvulsive therapy and cognition: effects of electrode placement, stimulus dosage and time.

    Science.gov (United States)

    Semkovska, Maria; Keane, Deborah; Babalola, Oyemi; McLoughlin, Declan M

    2011-06-01

    To clarify advantages of unilateral electrode placement as an optimisation technique for electroconvulsive therapy (ECT) for depression, aims were to meta-analyse unilateral ECT effects on cognitive performance relative to: (1) bitemporal electrode placement, (2) electrical dosage, and (3) time interval between final treatment and cognitive reassessment. Relevant electronic databases were systematically searched through May 2009, using the terms: "electroconvulsive therapy" and ["cogniti∗", "neuropsycholog∗", "memory", "attention", "executive", "spatial", or "intellectual"]. Inclusion criteria were: independent study of depressed patients receiving unilateral or bitemporal brief-pulse ECT; within-subjects design; use of objective cognitive assessments; available mean electrical dosage for unilateral samples. Standardized pre-post ECT weighted effect sizes were computed and pooled within 16 cognitive domains by a mixed-effects model. Thirty-nine studies (1415 patients) were meta-analysed. Up to three days after final treatment, unilateral ECT was associated with significantly smaller decreases in global cognition, delayed verbal memory retrieval, and autobiographical memory, compared to bitemporal ECT. Significant publication bias was found for autobiographical memory, favouring reporting of larger percentage loss. Higher unilateral ECT electrical dosage predicted larger decreases in verbal learning, delayed verbal memory retrieval, visual recognition, and semantic memory retrieval. When retested more than three days after completing ECT, no significant differences remained between the two electrode placements; for unilateral ECT, electrical dosage no longer predicted cognitive performance whereas increasing interval between final treatment and retesting predicted growing improvement in some variables. This interval is a more useful long-term predictor of cognitive function than electrode placement or electrical dosage following unilateral ECT. Copyright © 2010

  10. Stability of pharmaceutical salts in solid oral dosage forms.

    Science.gov (United States)

    Nie, Haichen; Byrn, Stephen R; Zhou, Qi Tony

    2017-08-01

    Using pharmaceutical salts in solid dosage forms can raise stability concerns, especially salt dissociation which can adversely affect the product performance. Therefore, a thorough understanding of the salt instability encountered in solid-state formulations is imperative to ensure the product quality. The present article uses the fundamental theory of acid base, ionic equilibrium, relationship of pH and solubility as a starting point to illustrate and interpret the salt formation and salt disproportionation in pharmaceutical systems. The criteria of selecting the optimal salt form and the underlying theory of salt formation and disproportionation are reviewed in detail. Factors influencing salt stability in solid dosage forms are scrutinized and discussed with the case studies. In addition, both commonly used and innovative strategies for preventing salt dissociations in formulation, on storage and during manufacturing will be suggested herein. This article will provide formulation scientists and manufacturing engineers an insight into the mechanisms of salt disproportionation and salt formation, which can help them to avoid and solve the instability issues of pharmaceutical salts in the product design.

  11. Simultaneous in vivo visualization and localization of solid oral dosage forms in the rat gastrointestinal tract by magnetic resonance imaging (MRI).

    Science.gov (United States)

    Christmann, V; Rosenberg, J; Seega, J; Lehr, C M

    1997-08-01

    Bioavailability of orally administered drugs is much influenced by the behavior, performance and fate of the dosage form within the gastrointestinal (GI) tract. Therefore, MRI in vivo methods that allow for the simultaneous visualization of solid oral dosage forms and anatomical structures of the GI tract have been investigated. Oral contrast agents containing Gd-DTPA were used to depict the lumen of the digestive organs. Solid oral dosage forms were visualized in a rat model by a 1H-MRI double contrast technique (magnetite-labelled microtablets) and a combination of 1H- and 19F-MRI (fluorine-labelled minicapsules). Simultaneous visualization of solid oral dosage forms and the GI environment in the rat was possible using MRI. Microtablets could reproducibly be monitored in the rat stomach and in the intestines using a 1H-MRI double contrast technique. Fluorine-labelled minicapsules were detectable in the rat stomach by a combination of 1H- and 19F-MRI in vivo. The in vivo 1H-MRI double contrast technique described allows solid oral dosage forms in the rat GI tract to be depicted. Solid dosage forms can easily be labelled by incorporating trace amounts of non-toxic iron oxide (magnetite) particles. 1H-MRI is a promising tool for observing such pharmaceutical dosage forms in humans. Combined 1H- and 19F-MRI offer a means of unambiguously localizing solid oral dosage forms in more distal parts of the GI tract. Studies correlating MRI examinations with drug plasma levels could provide valuable information for the development of pharmaceutical dosage forms.

  12. Mechanisms and evolutionary patterns of mammalian and avian dosage compensation.

    Directory of Open Access Journals (Sweden)

    Philippe Julien

    Full Text Available As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI. However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.

  13. SUPPRESSION OF DIELECTRONIC RECOMBINATION DUE TO FINITE DENSITY EFFECTS

    International Nuclear Information System (INIS)

    Nikolić, D.; Gorczyca, T. W.; Korista, K. T.; Ferland, G. J.; Badnell, N. R.

    2013-01-01

    We have developed a general model for determining density-dependent effective dielectronic recombination (DR) rate coefficients in order to explore finite-density effects on the ionization balance of plasmas. Our model consists of multiplying by a suppression factor those highly-accurate total zero-density DR rate coefficients which have been produced from state-of-the-art theoretical calculations and which have been benchmarked by experiment. The suppression factor is based upon earlier detailed collision-radiative calculations which were made for a wide range of ions at various densities and temperatures, but used a simplified treatment of DR. A general suppression formula is then developed as a function of isoelectronic sequence, charge, density, and temperature. These density-dependent effective DR rate coefficients are then used in the plasma simulation code Cloudy to compute ionization balance curves for both collisionally ionized and photoionized plasmas at very low (n e = 1 cm –3 ) and finite (n e = 10 10 cm –3 ) densities. We find that the denser case is significantly more ionized due to suppression of DR, warranting further studies of density effects on DR by detailed collisional-radiative calculations which utilize state-of-the-art partial DR rate coefficients. This is expected to impact the predictions of the ionization balance in denser cosmic gases such as those found in nova and supernova shells, accretion disks, and the broad emission line regions in active galactic nuclei.

  14. [Development and effectiveness of a drug dosage calculation training program using cognitive loading theory based on smartphone application].

    Science.gov (United States)

    Kim, Myoung Soo; Park, Jung Ha; Park, Kyung Yeon

    2012-10-01

    This study was done to develop and evaluate a drug dosage calculation training program using cognitive loading theory based on a smartphone application. Calculation ability, dosage calculation related self-efficacy and anxiety were measured. A nonequivalent control group design was used. Smartphone application and a handout for self-study were developed and administered to the experimental group and only a handout was provided for control group. Intervention period was 4 weeks. Data were analyzed using descriptive analysis, χ²-test, t-test, and ANCOVA with the SPSS 18.0. The experimental group showed more 'self-efficacy for drug dosage calculation' than the control group (t=3.82, psmartphone application is effective in improving dosage calculation related self-efficacy and calculation ability. Further study should be done to develop additional interventions for reducing anxiety.

  15. Dosage plasmatique et globulaire du magnesium dans l'exploration ...

    African Journals Online (AJOL)

    Objectives: The allergic rhinitis represents a real public health problem. The goal of this survey is to value the interest of the dosage plasmatical and globular of magnesium in the diagnosis of the allergic rhinitis. Materials and methods : Analytic and prospective survey of 80 files, on one period of 4 years and 5 months (from ...

  16. High-level face shape adaptation depends on visual awareness : Evidence from continuous flash suppression

    NARCIS (Netherlands)

    Stein, T.; Sterzer, P.

    When incompatible images are presented to the two eyes, one image dominates awareness while the other is rendered invisible by interocular suppression. It has remained unclear whether complex visual information can reach high-level processing stages in the ventral visual pathway during such

  17. Dosage of cesium 137 in radioactive wastes by the application of sodium tetraphenylborate; Dosage du cesium 137 dans les effluents radioactifs par le tetraphenylborate de sodium

    Energy Technology Data Exchange (ETDEWEB)

    Testemale, G; Girault, J [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1967-07-01

    A simple technique of the dosage of {sup 137}Cs has been developed. The technique consists in the formation of cesium tetraphenyl borate, followed by a double extraction with isoamyl acetate, and washing of the organic phase. The counting of known parts of the cesium solution assaying of its purity by {gamma} spectrometry enable the determination of the {sup 137}Cs. The yield is about 98 per cent. (authors) [French] Une technique simple du dosage du {sup 137}Cs a ete mise au point. Elle consiste en une double extraction du tetraphenylborate de cesium forme par l'acetate d'isoamyle suivie d'un lavage de la phase organique. Des comptages sur des parties aliquotes de la solution de cesium et un controle de purete par spectrometrie {gamma} permettent la determination de cet element. Rendement: environ 98 pour cent. (auteurs)

  18. Formation and suppression of acoustic memories during human sleep.

    Science.gov (United States)

    Andrillon, Thomas; Pressnitzer, Daniel; Léger, Damien; Kouider, Sid

    2017-08-08

    Sleep and memory are deeply related, but the nature of the neuroplastic processes induced by sleep remains unclear. Here, we report that memory traces can be both formed or suppressed during sleep, depending on sleep phase. We played samples of acoustic noise to sleeping human listeners. Repeated exposure to a novel noise during Rapid Eye Movements (REM) or light non-REM (NREM) sleep leads to improvements in behavioral performance upon awakening. Strikingly, the same exposure during deep NREM sleep leads to impaired performance upon awakening. Electroencephalographic markers of learning extracted during sleep confirm a dissociation between sleep facilitating memory formation (light NREM and REM sleep) and sleep suppressing learning (deep NREM sleep). We can trace these neural changes back to transient sleep events, such as spindles for memory facilitation and slow waves for suppression. Thus, highly selective memory processes are active during human sleep, with intertwined episodes of facilitative and suppressive plasticity.Though memory and sleep are related, it is still unclear whether new memories can be formed during sleep. Here, authors show that people could learn new sounds during REM or light non-REM sleep, but that learning was suppressed when sounds were played during deep NREM sleep.

  19. Short term and dosage influences of palm based medium- and long-chain triacylglycerols on body fat and blood parameters in C57BL/6J mice.

    Science.gov (United States)

    Lee, Yee-Ying; Tang, Teck-Kim; Ab Karim, Nur Azwani; Alitheen, Noorjahan Banu Mohamed; Lai, Oi-Ming

    2014-01-01

    Structured lipid medium- and long-chain triacylglycerols (MLCT) are claimed to be able to manage obesity. The present study investigated the body fat influence of enzymatically interesterifed palm-based medium- and long-chain triacylglycerols (P-MLCT) on diet-induced obesity (DIO) C57BL/6J mice compared with commercial MLCT oil (C-MLCT) and a control, which was the non enzymatically modified palm kernel and palm oil blend (PKO-PO blend). It also investigated the low fat and high fat effects of P-MLCT. DIO C57BL/6J mice were fed ad libitum with low fat (7%) and high fat (30%) experimental diets for 8 weeks before being sacrificed to obtain blood serum for analysis. From the results, there is a trend that P-MLCT fed mice were found to have the lowest body weight, body weight gain, total fat pad accumulation (perirenal, retroperitoneal, epididymal and mesenteric), total triglyceride levels and efficiency in controlling blood glucose level, compared with C-MLCT and the PKO-PO blend in both low fat and high fat diets. Nevertheless, the PKO-PO blend and P-MLCT caused significantly (P < 0.05) higher total cholesterol levels compared to C-MLCT. P-MLCT present in low fat and high fat dosage were shown to be able to suppress body fat accumulation. This effect is more prominent with the low fat dosage.

  20. Theoretical status of J/ψ suppression

    International Nuclear Information System (INIS)

    Gavin, S.

    1993-03-01

    High energy heavy ion collisions are expected to produce hadron densities far beyond the density in nuclei, ρ 0 = 0.16 fm -3 . Remarkably, no single measurement from the AGS and SPS light ion programs with projectiles A ≤ 32 stands out as unambiguous evidence of these extreme densities. To separate the high density signals from the background effects that result, e.g. from scattering with primary nucleons, careful systematic studies of hadron-nucleus, hA, and nucleus-nucleus, AB, data are needed. In this talk the author surveys the ongoing systematic study of the most notorious case in point -- J/ψ suppression. In principle, measurements of J/ψ suppression provide a probe of the densities obtained in AB collisions that is also sensitive to quark gluon plasma production. The latest results from SPS experiment NA38 reported by A. Romana in these proceedings show that the ratio of cross sections in the dimuon channel B μμ σ ψ /σ cont is reduced by a factor 0.50 ± 0.05 in central S+U compared to minimum bias pU collisions at 200 AGeV. This is precisely the sort of suppression that one expects if high densities are obtained. On the other hand, a target-mass dependence suggestive of this suppression is found in hA collisions where high densities are not expected. At 200 GeV, NA38 finds that B μμ σ ψ /σ cont falls to 0.84 ± 0.08 in pU compared to pCu. The hA suppression in this kinematic regime is likely due to a combination of nuclear effects: nucleon absorption and shadowing

  1. Suppression of beam-excited electron waves by an externally applied RF signal

    International Nuclear Information System (INIS)

    Fukumasa, Osamu; Itatani, Ryohei

    1980-11-01

    Suppression of the beam-excited electron wave in a bounded system is investigated in connection with the beam distribution function. Wave suppression has two different processes depending on whether injected beams are reflected at the other end or not. In the absence of reflected beam electrons, deformation of the beam distribution function is observed in relation to the suppression of the electron wave. However, when beam electrons are reflected, the external wave suppresses the electron wave but distribution function shows no appreciable change. These experimental results show that nonlinear behaviors of beam electrons, namely behaviors of reflected beams, are quite important for wave suppression. By using the method of partial simulation, interaction between two waves in the bounded system including nonlinear motions of beam electrons is studied numerically. Qualitative agreement between experimental and numerical results is obtained. (author)

  2. Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

    Directory of Open Access Journals (Sweden)

    Devyn D Gilette

    2014-04-01

    Full Text Available Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity.

  3. 76 FR 59023 - Oral Dosage Form New Animal Drugs; Tylosin

    Science.gov (United States)

    2011-09-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  4. 77 FR 3927 - Oral Dosage Form New Animal Drugs; Deracoxib

    Science.gov (United States)

    2012-01-26

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Deracoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  5. 76 FR 18648 - Oral Dosage Form New Animal Drugs; Robenacoxib

    Science.gov (United States)

    2011-04-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Robenacoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  6. 76 FR 40808 - Oral Dosage Form New Animal Drugs; Amprolium

    Science.gov (United States)

    2011-07-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  7. 77 FR 15960 - Oral Dosage Form New Animal Drugs; Pergolide

    Science.gov (United States)

    2012-03-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Pergolide AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  8. 75 FR 67031 - Oral Dosage Form New Animal Drugs; Domperidone

    Science.gov (United States)

    2010-11-01

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Domperidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  9. 76 FR 78149 - Oral Dosage Form New Animal Drugs; Estriol

    Science.gov (United States)

    2011-12-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

  10. Feedback Control of Sex Determination by Dosage Compensation Revealed through Caenorhabditis Elegans Sdc-3 Mutations

    OpenAIRE

    DeLong, L.; Plenefisch, J. D.; Klein, R. D.; Meyer, B. J.

    1993-01-01

    In Caenorhabditis elegans, sex determination and dosage compensation are coordinately controlled through a group of genes that respond to the primary sex determination signal. Here we describe a new gene, sdc-3, that also controls these processes. In contrast to previously described genes, the sex determination and dosage compensation activities of sdc-3 are separately mutable, indicating that they function independently. Paradoxically, the sdc-3 null phenotype fails to reveal the role of sdc...

  11. Radiation doses for pediatric nuclear medicine studies: comparing the North American consensus guidelines and the pediatric dosage card of the European Association of Nuclear Medicine.

    Science.gov (United States)

    Grant, Frederick D; Gelfand, Michael J; Drubach, Laura A; Treves, S Ted; Fahey, Frederic H

    2015-04-01

    Estimated radiation dose is important for assessing and communicating the risks and benefits of pediatric nuclear medicine studies. Radiation dose depends on the radiopharmaceutical, the administered activity, and patient factors such as age and size. Most radiation dose estimates for pediatric nuclear medicine have not been based on administered activities of radiopharmaceuticals recommended by established practice guidelines. The dosage card of the European Association of Nuclear Medicine (EANM) and the North American consensus guidelines each provide recommendations of administered activities of radiopharmaceuticals in children, but there are substantial differences between these two guidelines. For 12 commonly performed pediatric nuclear medicine studies, two established pediatric radiopharmaceutical administration guidelines were used to calculate updated radiation dose estimates and to compare the radiation exposure resulting from the recommendations of each of the guidelines. Estimated radiation doses were calculated for 12 common procedures in pediatric nuclear medicine using administered activities recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North American consensus guidelines for radiopharmaceutical administered activities in pediatrics. Based on standard models and nominal age-based weights, radiation dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult. The resulting effective doses were compared, with differences greater than 20% considered significant. Following either the EANM dosage card or the 2010 North American guidelines, the highest effective doses occur with radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases, following the North American consensus guidelines would result in a substantially higher radiation dose. The guidelines of the EANM dosage card would lead to a substantially higher radiation dose in 39% of all cases, and in 62% of cases in which patients

  12. Radiation doses for pediatric nuclear medicine studies: comparing the North American consensus guidelines and the pediatric dosage card of the European Association of Nuclear Medicine

    International Nuclear Information System (INIS)

    Grant, Frederick D.; Drubach, Laura A.; Treves, S. Ted; Fahey, Frederic H.; Gelfand, Michael J.

    2015-01-01

    Estimated radiation dose is important for assessing and communicating the risks and benefits of pediatric nuclear medicine studies. Radiation dose depends on the radiopharmaceutical, the administered activity, and patient factors such as age and size. Most radiation dose estimates for pediatric nuclear medicine have not been based on administered activities of radiopharmaceuticals recommended by established practice guidelines. The dosage card of the European Association of Nuclear Medicine (EANM) and the North American consensus guidelines each provide recommendations of administered activities of radiopharmaceuticals in children, but there are substantial differences between these two guidelines. For 12 commonly performed pediatric nuclear medicine studies, two established pediatric radiopharmaceutical administration guidelines were used to calculate updated radiation dose estimates and to compare the radiation exposure resulting from the recommendations of each of the guidelines. Estimated radiation doses were calculated for 12 common procedures in pediatric nuclear medicine using administered activities recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North American consensus guidelines for radiopharmaceutical administered activities in pediatrics. Based on standard models and nominal age-based weights, radiation dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult. The resulting effective doses were compared, with differences greater than 20% considered significant. Following either the EANM dosage card or the 2010 North American guidelines, the highest effective doses occur with radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases, following the North American consensus guidelines would result in a substantially higher radiation dose. The guidelines of the EANM dosage card would lead to a substantially higher radiation dose in 39% of all cases, and in 62% of cases in which patients

  13. Dosage of trace carbon in sodium (1963); Dosage de traces de carbone dans le sodium (1963)

    Energy Technology Data Exchange (ETDEWEB)

    Sannier, J; Vasseur, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1963-07-01

    A wet method for dosing carbon in sodium has been developed. The carbon is oxidised in a vacuum using Van SLYKE'S solution. The carbonic acid formed is measured volumetrically; its purity can be controlled by chromatographic analysis. The results obtained show that this method makes it possible to measure carbon in concentrations of about 10 ppm. (authors) [French] Une methode de dosage par voie humide du carbone dans le sodium a ete mise au point. L'oxydation du carbone par la solution de Van SLYKE est realisee sous vide. Le gaz carbonique forme est dose volumetriquement; sa purete peut etre controlee par analyse chromatographique. Les resultats obtenus montrent que cette methode permet de doser des teneurs en carbone de l'ordre de 10 ppm. (auteurs)

  14. Comparative pharmacokinetic study of dosage forms with morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate

    Directory of Open Access Journals (Sweden)

    I. V. Bushueva

    2014-12-01

    ] acetate elimination from the body of the animal occurs within 1 hour, and then only trace amount of the drug substanceis detected in serum. After oral and rectal dosage forms of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate its maximum concentration in the blood of laboratory animals is recorded at 60 minutes after administration of the capsules and suppositories respectively. Thereafter, for 2-2, 5 it is supported at a high level. At the same time, no significant differences in the kinetics of the drug administered dose. 24 hours after single oral administration and rectal capsules and suppositories of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate is not detected in the serum. Comparative analysis of the pharmacokinetics of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate depending on the kind of administration and the dosage form shows that after oral administration in capsule form, and rectal administration as a suppository absorption rate constants, elimination, half-life periods floor suction and depending on the dose administered differ slightly. Also, almost no relationship between dose and orally administered rectally morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate and total quantities (of plasma clearance, since the difference between the drug administered in doses of 5 times the value of the latter increased only 1.2 times. Degree of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate absolute bioavailability after oral and rectal administration, is practically independent from the dose. The magnitude of this indicator for rectal suppository almost 3 times higher than that for oral capsules of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate. This indicates the great promise of his rectal dosage form. Conclusion. The degree of its absolute bioavailability for rectal dosage form doesn’t depend on administered dose and is nearly twice higher than for the oral solid

  15. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

    NARCIS (Netherlands)

    Plöger, Gerlinde F; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D I R K W; Langguth, Peter; Mehta, Mehul U; Parr, Alan; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Dressman, Jennifer B

    2018-01-01

    Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To clarify the Biopharmaceutics Classification System (BCS) classification, experimental solubility and

  16. Pharmaceutical development of an intravenous dosage form of diacetylmorphine hydrochloride

    NARCIS (Netherlands)

    Klous, Marjolein G.; Nuijen, Bastiaan; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

    2004-01-01

    A solid dosage form for multiple use was developed for parenteral administration of diacetylmorphine in a clinical trial on co-prescription of heroin to heroin addicts. A 300-mg/mL diacetylmorphine hydrochloride solution was lyophilised as 10-mL aliquots in 30-mL glass vials, to be reconstituted to

  17. Preparation, extraction and dosage of labelled cholesterol (D and C{sup 14}); Preparation, extraction et dosage de cholesterol marque (D et C{sup 14})

    Energy Technology Data Exchange (ETDEWEB)

    Bugnard, L; Chevallier, F; Coursaget, J [Commissariat a l' Energie Atomique, Saclay(France). Centre d' Etudes Nucleaires

    1953-07-01

    We returned in this note the techniques that we used for the preparation of labelled cholesterol. The chemical exchange of hydrogen enabling to contain deutero-cholesterol until 4 percent deuterium. The biologic synthesis, done on living rats or on their liver maintained in survival, permits, on the other hand, to get active cholesterol from acetate of containing sodium of the carbon 14. We indicated the techniques of extraction and dosage of the marked cholesterol. The radioactivity is measured with a Geiger-Muller counter. (M.B.) [French] Nous avons rapporte dans cette note les techniques que nous avons utilisees pour la preparation de cholesterol marque. L'echange chimique d'hydrogene conduit a du deuterio-cholesterol pouvant contenir jusqu'a 4 pour cent de deuterium. La synthese biologique, effectuee sur des rats vivants ou sur leur foie maintenu en survie, permet, d'autre part, d'obtenir du cholesterol radio-actif a partir d'acetate de sodium contenant du carbone 14. Nous avons indique les techniques d'extraction et de dosage du cholesterol marque. Sa radioactivite est mesuree au compteur de Geiger-Muller. (M.B.)

  18. Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

    International Nuclear Information System (INIS)

    Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R.

    1992-01-01

    Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.)

  19. Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

    Energy Technology Data Exchange (ETDEWEB)

    Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R. (Pharmaceutical Profiles Ltd., Nottingham (United Kingdom))

    1992-11-01

    Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.).

  20. ORODISPERSIBLE TABLET: A Patient Friendly Dosage Form (a Review

    Directory of Open Access Journals (Sweden)

    C. K. Rameesa

    2015-03-01

    Full Text Available Background: The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to superdisintegrants in the formulation. Thus this type of drug delivery helps a proper per oral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method is the direct compression method. Other special methods are Freeze Drying,Tablet Molding, Sublimation, Spray Drying, Mass extrusion, Phase transition process, etc. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test and dissolution test.

  1. Suppression of radiation mutagenesis by dactinomycin in Chinese hamster cells

    International Nuclear Information System (INIS)

    Tokita, N.; Capenter, S.G.; Chen, D.J.; MacInnes, M.A.; Raju, M.R.

    1985-01-01

    Dactinomycin (AMD) suppression of radiation mutagenesis was investigated using an in vitro mutation assay (6-thioguanine resistance) in Chinese hamster ovary cells. Cells were exposed to acute single doses of x rays followed by 1 hr-treatment with 0.1 or 1 μg/ml AMD. The cell survival curves plotted as a function of x-ray doses were similar for radiation alone and radiation plus AMD. The results suggest that AMD treatment was only slightly mutagenic, however, when given immediately after irradiation, it suppressed radiatiion mutagenesis at higher x-ray dose regions (below 10% survival levels). Higher AMD concentrations appeared more suppressive than lower concentrations. Dose-response data analyzed based on Poisson distribution models suggest the stochastic dependence of x-ray mutagenesis and AMD cytotoxity

  2. Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms.

    Science.gov (United States)

    Goole, J; Vanderbist, F; Amighi, K

    2007-04-04

    This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.

  3. Growth of Murine Splenic Tissue Is Suppressed by Lymphotoxin β-Receptor Signaling (LTβR) Originating from Splenic and Non-Splenic Tissues

    DEFF Research Database (Denmark)

    Milićević, Novica M; Nohroudi, Klaus; Schmidt, Friederike

    2016-01-01

    LTβR signaling. Two-dimensional differential gel electrophoresis and subsequent mass spectrometry of stromal splenic tissue was applied to screen for potential factors mediating the LTβR dependent suppressive activity. Thus, LTβR dependent growth suppression is involved in regulating the size...

  4. An Allergic Lung Microenvironment Suppresses Carbon Nanotube-Induced Inflammasome Activation via STAT6-Dependent Inhibition of Caspase-1.

    Directory of Open Access Journals (Sweden)

    Kelly A Shipkowski

    pro-fibrogenic cytokine mRNAs.These data indicate that Th2 cytokines suppress MWCNT-induced inflammasome activation via STAT6-dependent down-regulation of pro-caspase-1 and suggest that suppression of inflammasome activation and IL-1β by an allergic lung microenvironment is a mechanism through which MWCNTs exacerbate allergen-induced airway fibrosis.

  5. Suppression of [sup 125]I-uptake in mouse thyroid by seaweed feeding; Possible preventative effect of dietary seaweed on internal radiation injury of the thyroid by radioactive iodine

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Hiroko; Yamamoto, Ichiro (Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Hygienic Sciences)

    1992-12-01

    We conducted an animal experiment to determine how dietary seaweeds rich in iodine and dietary fibers suppress radioactive iodine uptake by the thyroid, using mice and four kinds of experimental diets, three with 1% or 2% powdered fronds of the kelp Laminaria religiosa and 2% powdered laver Porphyra yezoensis, and one with cellulose. Iodine content of a hot-water extract of the kelp was 0.530[+-]0.001%, and its dietary fiber (DF) values were 52.8[+-]1.2%. Iodine in an extract of the laver was 0.008[+-]0.001%, and its DF values were 41.4%[+-]0.7%. A statistically significant reduction of [sup 125]I uptake by the thyroid, 3 hours after intragastric administration of the radionuclide at a dosage of 18.5 kBq or 185 kBq in 0.3 ml aqueous solution per mouse, was observed in mice previously fed the experimental diets containing 1% and 2% kelp during periods varying from 24 hours to 7 days. The degree of the suppression was observed to depend on the amount of iodine in the diet or in the injected sample, no matter whether organic or inorganic, judging from the results of an additional experiment. Thus, we conclude that previously fed iodine-rich material, especially dietary seaweeds rich in iodine and other minerals, vitamins, and [beta]-carotene, such as kelps or laver supplemented with inorganic iodine, may be effective in prevention of internal radiation injury of the thyroid. (author).

  6. Context shapes social judgments of positive emotion suppression and expression.

    Science.gov (United States)

    Kalokerinos, Elise K; Greenaway, Katharine H; Casey, James P

    2017-02-01

    It is generally considered socially undesirable to suppress the expression of positive emotion. However, previous research has not considered the role that social context plays in governing appropriate emotion regulation. We investigated a context in which it may be more appropriate to suppress than express positive emotion, hypothesizing that positive emotion expressions would be considered inappropriate when the valence of the expressed emotion (i.e., positive) did not match the valence of the context (i.e., negative). Six experiments (N = 1,621) supported this hypothesis: when there was a positive emotion-context mismatch, participants rated targets who suppressed positive emotion as more appropriate, and evaluated them more positively than targets who expressed positive emotion. This effect occurred even when participants were explicitly made aware that suppressing targets were experiencing mismatched emotion for the context (e.g., feeling positive in a negative context), suggesting that appropriate emotional expression is key to these effects. These studies are among the first to provide empirical evidence that social costs to suppression are not inevitable, but instead are dependent on context. Expressive suppression can be a socially useful emotion regulation strategy in situations that call for it. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. Spironolactone induces apoptosis in human mononuclear cells. Association between apoptosis and cytokine suppression

    DEFF Research Database (Denmark)

    Mikkelsen, Martin; Sønder, S U; Nersting, J

    2006-01-01

    preceding apoptosis. An association between the two effects was also seen when testing several SPIR analogues. Contrary to TNF-alpha, the levels of IL-1beta increased in SPIR-treated cultures. However, the amount of IL-1beta in the supernatants depended upon the order of SPIR and LPS addition, as IL-1beta....... In conclusion, suppression of cytokine production by SPIR may be associated with its apoptotic potential, either directly (apoptosis is a consequence of suppressed cytokine production, or vice-versa) or indirectly (suppressed cytokine production and apoptosis are parallel but otherwise unrelated phenomena)....

  8. Incomplete sex chromosome dosage compensation in the Indian meal moth, Plodia interpunctella, based on de novo transcriptome assembly.

    Science.gov (United States)

    Harrison, Peter W; Mank, Judith E; Wedell, Nina

    2012-01-01

    Males and females experience differences in gene dose for loci in the nonrecombining region of heteromorphic sex chromosomes. If not compensated, this leads to expression imbalances, with the homogametic sex on average exhibiting greater expression due to the doubled gene dose. Many organisms with heteromorphic sex chromosomes display global dosage compensation mechanisms, which equalize gene expression levels between the sexes. However, birds and Schistosoma have been previously shown to lack chromosome-wide dosage compensation mechanisms, and the status in other female heterogametic taxa including Lepidoptera remains unresolved. To further our understanding of dosage compensation in female heterogametic taxa and to resolve its status in the lepidopterans, we assessed the Indian meal moth, Plodia interpunctella. As P. interpunctella lacks a complete reference genome, we conducted de novo transcriptome assembly combined with orthologous genomic location prediction from the related silkworm genome, Bombyx mori, to compare Z-linked and autosomal gene expression levels for each sex. We demonstrate that P. interpunctella lacks complete Z chromosome dosage compensation, female Z-linked genes having just over half the expression level of males and autosomal genes. This finding suggests that the Lepidoptera and possibly all female heterogametic taxa lack global dosage compensation, although more species will need to be sampled to confirm this assertion.

  9. The Effect of High and Low Antiepileptic Drug Dosage on Simulated Driving Performance in Person's with Seizures: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Alexander M. Crizzle

    2015-10-01

    Full Text Available Background: Prior studies examining driving performance have not examined the effects of antiepileptic drugs (AED’s or their dosages in persons with epilepsy. AED’s are the primary form of treatment to control seizures, but they are shown to affect cognition, attention, and vision, all which may impair driving. The purpose of this study was to describe the characteristics of high and low AED dosages on simulated driving performance in persons with seizures. Method: Patients (N = 11; mean age 42.1 ± 6.3; 55% female; 100% Caucasian were recruited from the Epilepsy Monitoring Unit and had their driving assessed on a simulator. Results: No differences emerged in total or specific types of driving errors between high and low AED dosages. However, high AED drug dosage was significantly associated with errors of lane maintenance (r = .67, p < .05 and gap acceptance (r = .66, p < .05. The findings suggest that higher AED dosages may adversely affect driving performance, irrespective of having a diagnosis of epilepsy, conversion disorder, or other medical conditions. Conclusion: Future studies with larger samples are required to examine whether AED dosage or seizure focus alone can impair driving performance in persons with and without seizures.

  10. In vivo evaluation of dosage forms: application of gamma scintigraphy to non-enteral routes of administration.

    Science.gov (United States)

    Meseguer, G; Gurny, R; Buri, P

    1994-01-01

    The trend to deliver drugs to defined areas of the body involves sophisticated carriers systems. In addition to the in vitro drug release profile one must be aware of the in vivo behaviour of the dosage form and the drug. Gamma scintigraphy is an elegant way to gain insights of the actual in vivo distribution pattern of dosage forms. This technique relies on the use of radioactive tracers included into the medicament and selected so as to enable an optimum detection by a gamma ray camera. The choice of a convenient label enables the in vivo determination of the targeting of the formulation administered through a large number of routes. The present paper reviews applications of gamma scintigraphy for the evaluation of dosage forms administered by the parenteral, rectal, buccal, nasal, pulmonary, and ophthalmic routes.

  11. LABORATORY PROTECTION RATE OF TORN BEDNETS TREATED WITH THREE DOSAGES OF PYRETHROIDE AGAINST ANOPHELES CULICIFACIES

    Directory of Open Access Journals (Sweden)

    G. Babaee

    2007-05-01

    Full Text Available Evaluated under laboratory condition. The objective of the present study was to observe the effect of impregnated torn bednets on the number of bites by An. culicifacies A glass made tunnel test was designed to The effect of torn bednets treated with three dosages of cyfluthrin 5% EW, were induce hungry female mosquitoes to pass through holes cut in the pyrethroid treated nets. A guinea pig used as bait to attract mosquitoes through circular holes in the netting. With untreated netting, 72-87% of laboratory-reared females passed through the holes overnight, 64-92% blood-fed successfully and 0.3/9-4/3% died. When the netting was treated with cyfluthrin at doses of 25, 50 and 100 mg a.i./m2, the entry Index (the proportions that passed through the holes overnight were 43.37%, 42.82% and 24.72%; mortality rates were 66.31%, 81.45% and 95.99%; and the feeding rate were 45%, 27% and 3%. In conclusion it should be stressed that efficacy of pyrethroid impregnated bednets using “Tunnel Tests” showing acceptable protection rate both in lower and higher dosages as well as cause dead in the blood-fed mosquitoes. In addition, the higher dosages of these three dosages pyrethroid provided good levels of protection against An. culicifacies.

  12. Contraceptive Use Affects Overall Olfactory Performance: Investigation of Estradiol Dosage and Duration of Intake.

    Directory of Open Access Journals (Sweden)

    Kathrin Kollndorfer

    Full Text Available The influence of female sex steroids on cognitive performance and sensory perception has been investigated for decades. However, previous research that studied olfaction revealed inconsistent results. The main aim of this study was to investigate the effects of different ethinyl estradiol (EE concentrations of oral contraceptives and duration of intake on olfactory function. Forty-two healthy women, with regular intake of either high or low EE dosage over at least one year and up to 15 years participated in this study. Results revealed a significant concordance between a priori categorization in the two groups with high and low EE dosage and data-driven hierarchical clustering (p = 0.008. Furthermore, significantly higher olfactory performance was observed in women using low-dose products compared to women using high-dosed products (p = 0.019. These findings indicate different effects of pill use with regard to EE concentration. We therefore strongly recommend the acquisition of information about EE dosage of oral contraceptives to reduce potential confounding factors when investigating sensory systems.

  13. 75 FR 21162 - Certain Other Dosage Form New Animal Drugs; Detomidine

    Science.gov (United States)

    2010-04-23

    .... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine AGENCY: Food and Drug... NADA provides for veterinary prescription use of detomidine hydrochloride oromucosal gel for sedation... prescription use of DORMOSEDAN GEL (detomidine hydrochloride) for sedation and restraint of horses. The...

  14. Arsenic removal from groundwater using iron electrocoagulation: effect of charge dosage rate.

    Science.gov (United States)

    Amrose, Susan; Gadgil, Ashok; Srinivasan, Venkat; Kowolik, Kristin; Muller, Marc; Huang, Jessica; Kostecki, Robert

    2013-01-01

    We demonstrate that electrocoagulation (EC) using iron electrodes can reduce arsenic below 10 μg/L in synthetic Bangladesh groundwater and in real groundwater from Bangladesh and Cambodia, while investigating the effect of operating parameters that are often overlooked, such as charge dosage rate. We measure arsenic removal performance over a larger range of current density than in any other single previous EC study (5000-fold: 0.02 - 100 mA/cm(2)) and over a wide range of charge dosage rates (0.060 - 18 Coulombs/L/min). We find that charge dosage rate has significant effects on both removal capacity (μg-As removed/Coulomb) and treatment time and is the appropriate parameter to maintain performance when scaling to different active areas and volumes. We estimate the operating costs of EC treatment in Bangladesh groundwater to be $0.22/m(3). Waste sludge (~80 - 120 mg/L), when tested with the Toxic Characteristic Leachate Protocol (TCLP), is characterized as non-hazardous. Although our focus is on developing a practical device, our results suggest that As[III] is mostly oxidized via a chemical pathway and does not rely on processes occurring at the anode. Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Environmental Science and Health, Part A, to view the free supplemental file.

  15. Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

    Science.gov (United States)

    Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

    2013-10-01

    Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

  16. Enhancement and suppression in the visual field under perceptual load.

    Science.gov (United States)

    Parks, Nathan A; Beck, Diane M; Kramer, Arthur F

    2013-01-01

    The perceptual load theory of attention proposes that the degree to which visual distractors are processed is a function of the attentional demands of a task-greater demands increase filtering of irrelevant distractors. The spatial configuration of such filtering is unknown. Here, we used steady-state visual evoked potentials (SSVEPs) in conjunction with time-domain event-related potentials (ERPs) to investigate the distribution of load-induced distractor suppression and task-relevant enhancement in the visual field. Electroencephalogram (EEG) was recorded while subjects performed a foveal go/no-go task that varied in perceptual load. Load-dependent distractor suppression was assessed by presenting a contrast reversing ring at one of three eccentricities (2, 6, or 11°) during performance of the go/no-go task. Rings contrast reversed at 8.3 Hz, allowing load-dependent changes in distractor processing to be tracked in the frequency-domain. ERPs were calculated to the onset of stimuli in the load task to examine load-dependent modulation of task-relevant processing. Results showed that the amplitude of the distractor SSVEP (8.3 Hz) was attenuated under high perceptual load (relative to low load) at the most proximal (2°) eccentricity but not at more eccentric locations (6 or 11°). Task-relevant ERPs revealed a significant increase in N1 amplitude under high load. These results are consistent with a center-surround configuration of load-induced enhancement and suppression in the visual field.

  17. Enhancement and Suppression in the Visual Field under Perceptual Load

    Directory of Open Access Journals (Sweden)

    Nathan A Parks

    2013-05-01

    Full Text Available The perceptual load theory of attention proposes that the degree to which visual distractors are processed is a function of the attentional demands of a task – greater demands increase filtering of irrelevant distractors. The spatial configuration of such filtering is unknown. Here, we used steady-state visual evoked potentials (SSVEPs in conjunction with time-domain event-related potentials (ERPs to investigate the distribution of load-induced distractor suppression and task-relevant enhancement in the visual field. Electroencephalogram (EEG was recorded while subjects performed a foveal go/no-go task that varied in perceptual load. Load-dependent distractor suppression was assessed by presenting a contrast reversing ring at one of three eccentricities (2°, 6°, or 11° during performance of the go/no-go task. Rings contrast reversed at 8.3 Hz, allowing load-dependent changes in distractor processing to be tracked in the frequency-domain. ERPs were calculated to the onset of stimuli in the load task to examine load-dependent modulation of task-relevant processing. Results showed that the amplitude of the distractor SSVEP (8.3Hz was attenuated under high perceptual load (relative to low load at the most proximal (2° eccentricity but not at more eccentric locations (6˚ or 11˚. Task-relevant ERPs revealed a significant increase in N1 amplitude under high load. These results are consistent with a center-surround configuration of load-induced enhancement and suppression in the visual field.

  18. The accuracy of warfarin dosage based on VKORC1 and CYP2C9 phenotypes in a Chinese population

    Directory of Open Access Journals (Sweden)

    Agustinus Wijaya

    2012-05-01

    Full Text Available Background: The aim of this study is to assess the accuracy of warfarin dosage based on VKORC1 and CYP2C9 genotype in Chinese population.Methods: Blood samples were taken from 37 patients. We compared the warfarin dosage obtained from genotype (according to www.warfarindosing.org and treatment dosage with international normalized ratio (INR value within 2.0-3.0.Results: The majority of Chinese people in our study are VKORC1 homozygous AA (89.2%, rarely VKORC1 heterozygous AG and we cannot find a patient with homozygous GG. For CYP2C9 genotype, most patients have the wildtype variants (CYP2C9*2 CC and CYP2C9*3 AA. The warfarin dosage for patients with VKORC1 AA and CYP2C9*3 AC is lower than for patients with other genotype variants.Conclusion: There is no significant difference between pharmacogenetic algorithm (www.warfarindosing.org and our treatment dosage. Our conclusion is that the pharmacogenetic algorithm is accurate to predict the warfarin dose. (Med J Indones. 2012;21:108-12Keywords: CYP2C9, pharmacogenetic algorithm, VKORC1, warfarin

  19. Dosage Compensation of an Aneuploid Genome in Mouse Spermatogenic Cells

    Czech Academy of Sciences Publication Activity Database

    Jansa, Petr; Homolka, David; Blatný, Radek; Mistrik, M.; Bartek, Jiří; Forejt, Jiří

    2014-01-01

    Roč. 90, č. 6 (2014), 124/1-124/9 ISSN 0006-3363 R&D Projects: GA ČR GA13-08078S Institutional support: RVO:68378050 Keywords : gene dosage * male sterility * segmental trisomy * meiotic silencing of unsynapsed chromatin * DOWN-SYNDROME * MAMMALIAN MEIOSIS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.318, year: 2014

  20. Dosage Compensation of an Aneuploid Genome in Mouse Spermatogenic Cells

    Czech Academy of Sciences Publication Activity Database

    Jansa, Petr; Homolka, David; Blatný, Radek; Mistrik, M.; Bartek, Jiří; Forejt, Jiří

    2014-01-01

    Roč. 90, č. 6 (2014), 124/1-124/9 ISSN 0006-3363 R&D Projects: GA ČR GA13-08078S Institutional support: RVO:68378050 Keywords : gene dosage * male sterility * segmental trisomy * meiotic silencing of unsynapsed chromatin * DOWN - SYNDROME * MAMMALIAN MEIOSIS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.318, year: 2014

  1. Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

    Science.gov (United States)

    Gillette, Devyn D.; Curry, Heather M.; Cremer, Thomas; Ravneberg, David; Fatehchand, Kavin; Shah, Prexy A.; Wewers, Mark D.; Schlesinger, Larry S.; Butchar, Jonathan P.; Tridandapani, Susheela; Gavrilin, Mikhail A.

    2014-01-01

    Background: Human monocyte inflammatory responses differ between virulent and attenuated Francisella infection. Results: A mixed infection model showed that the virulent F. tularensis Schu S4 can attenuate inflammatory cytokine responses to the less virulent F. novicida in human monocytes. Conclusion: F. tularensis dampens inflammatory response by an active process. Significance: This suppression may contribute to enhanced pathogenicity of F. tularensis. Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity. PMID:24783062

  2. Biowaiver monographs for immediate release solid oral dosage forms: efavirenz.

    Science.gov (United States)

    Cristofoletti, Rodrigo; Nair, Anita; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Dressman, Jennifer B

    2013-02-01

    Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence testing for the approval of immediate-release (IR) solid oral dosage forms containing efavirenz as the only active pharmaceutical ingredient (API) are reviewed. Because of lack of conclusive data about efavirenz's permeability and its failure to comply with the "high solubility" criteria according to the Biopharmaceutics Classification System (BCS), the API can be classified as BCS Class II/IV. In line with the solubility characteristics, the innovator product does not meet the dissolution criteria for a "rapidly dissolving product." Furthermore, product variations containing commonly used excipients or in the manufacturing process have been reported to impact the rate and extent of efavirenz absorption. Despite its wide therapeutic index, subtherapeutic levels of efavirenz can lead to treatment failure and also facilitate the emergence of efavirenz-resistant mutants. For all these reasons, a biowaiver for IR solid oral dosage forms containing efavirenz as the sole API is not scientifically justified for reformulated or multisource drug products. Copyright © 2012 Wiley Periodicals, Inc.

  3. Neural Correlates of Direct and Indirect Suppression of Autobiographical Memories.

    Science.gov (United States)

    Noreen, Saima; O'Connor, Akira R; MacLeod, Malcolm D

    2016-01-01

    Research indicates that there are two possible mechanisms by which particular target memories can be intentionally forgotten. Direct suppression, which involves the suppression of the unwanted memory directly, and is dependent on a fronto-hippocampal modulatory process, and, memory substitution, which includes directing one's attention to an alternative memory in order to prevent the unwanted memory from coming to mind, and involves engaging the caudal prefrontal cortex (cPFC) and the mid-ventrolateral prefrontal cortex (VLPFC) regions. Research to date, however, has investigated the neural basis of memory suppression of relatively simple information. The aim of the current study was to use fMRI to identify the neural mechanisms associated with the suppression of autobiographical memories. In the present study, 22 participants generated memories in response to a series of cue words. In a second session, participants learnt these cue-memory pairings, and were subsequently presented with a cue word and asked either to recall (think) or to suppress (no-think) the associated memory, or to think of an alternative memory in order to suppress the original memory (memory-substitution). Our findings demonstrated successful forgetting effects in the no-think and memory substitution conditions. Although we found no activation in the dorsolateral prefrontal cortex, there was reduced hippocampal activation during direct suppression. In the memory substitution condition, however, we failed to find increased activation in the cPFC and VLPFC regions. Our findings suggest that the suppression of autobiographical memories may rely on different neural mechanisms to those established for other types of material in memory.

  4. Neural Correlates of Direct and Indirect Suppression of Autobiographical Memories

    Directory of Open Access Journals (Sweden)

    Saima eNoreen

    2016-03-01

    Full Text Available Research indicates that there are two possible mechanisms by which particular target memories can be intentionally forgotten. Direct suppression, which involves the suppression of the unwanted memory directly, and is dependent on a fronto-hippocampal modulatory process, and, memory substitution, which includes directing one's attention to an alternative memory in order to prevent the unwanted memory from coming to mind, and involves engaging the caudal prefrontal cortex (cPFC and the mid-ventrolateral prefrontal cortex (VLPFC regions. Research to date, however, has investigated the neural basis of memory suppression of relatively simple information. The aim of the current study was to use fMRI to identify the neural mechanisms associated with the suppression of autobiographical memories. In the present study, 22 participants generated memories in response to a series of cue words. In a second session, participants learnt these cue-memory pairings, and were subsequently presented with a cue word and asked either to recall (think or to suppress (no-think the associated memory, or to think of an alternative memory in order to suppress the original memory (memory-substitution. Our findings demonstrated successful forgetting effects in the no-think and memory substitution conditions. Although we found no activation in the dorsolateral prefrontal cortex there was reduced hippocampal activation during direct suppression. In the memory substitution condition, however, we failed to find increased activation in the cPFC and VLPFC regions. Our findings suggest that the suppression of autobiographical memories may rely on different neural mechanisms to those established for other types of material in memory.

  5. Work Stress and Depressive Symptoms in Fishermen With a Smoking Habit: A Mediator Role of Nicotine Dependence and Possible Moderator Role of Expressive Suppression and Cognitive Reappraisal.

    Science.gov (United States)

    Jiang, Hongjuan; Li, Sailan; Yang, Juan

    2018-01-01

    This study examined pathways of influence between work stress, depressive symptoms, nicotine dependence, expressive suppression, and cognitive reappraisal in fishermen with smoking habits in Qionghai, Hainan province, China (N = 1068). These fishermen responded to multiple assessments a week before leaving on a deep-sea fishing trip, including a Mental Stressor Investigation Questionnaire (MSIQ), the Center for Epidemiological Studies Depression Scale (CES-D), the Russell Reason for Smoking Questionnaire (RRSQ), and an Emotion Regulation Questionnaire (ERQ). Structural equation modeling (SEM) analyses of the collected data in Mplus 7 showed that work stress and nicotine dependence were independent predictors of depressive symptoms. The relationship between work stress and depressive symptoms was found to be partially mediated by nicotine dependence and be moderated by cognitive reappraisal. The evidence suggests it advantageous to examine the need of work stress, nicotine dependence, and cognitive reappraisal when attempting to understand depressive symptoms in fishermen with a smoking habit. These findings suggest that improving nicotine dependence through work stress management and training in cognitive reappraisal could be utilized as effective modalities for improving depressive symptoms.

  6. Laūq: A Sustained-Release Dosage Form for Respiratory Disorders in Traditional Persian Medicine.

    Science.gov (United States)

    Karegar-Borzi, Hossein; Salehi, Mehdi; Rahimi, Roja

    2016-01-01

    Laūq is a pharmaceutical dosage form that had been mainly used for the treatment of various respiratory disorders in traditional Persian medicine. It is important from 2 aspects: a dosage form with efficient and optimum delivery of drugs to the respiratory tract and biological effects of its ingredients. Natural medicine in laūq has been demonstrated to act in respiratory disorders by their antitussive, antiallergic, anti-inflammatory, antioxidant, spasmolytic, and antibacterial activities. Some of these natural remedies act by most of the mentioned mechanisms such as Cydonia oblonga, Glycyrrhiza glabra, Crocus sativus, Hyssopus officinalis, Foeniculum vulgare, and honey. However, the evidence is limited including Cassia fistula, Papaver somniferum, and Drimia maritima. According to positive pharmacokinetic and pharmacodynamic aspects of laūqs, they may be considered as efficient dosage forms for delivery of drugs to the respiratory tract. For better compatibility of patients, it could be substituted laūqs with newer drug delivery systems like lozenges. © The Author(s) 2015.

  7. 78 FR 30197 - Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin

    Science.gov (United States)

    2013-05-22

    ...-0002] Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin AGENCY: Food and Drug Administration...- Tallaght, Dublin Oral Drops. 940. 24, Ireland. 200-551........ Putney, Inc., 400 Enrofloxacin Original....812 Enrofloxacin. (a) Specifications. Each tablet contains 22.7, 68.0, or 136.0 milligrams (mg) of...

  8. Epstein-Barr Virus MicroRNA miR-BART20-5p Suppresses Lytic Induction by Inhibiting BAD-Mediated caspase-3-Dependent Apoptosis.

    Science.gov (United States)

    Kim, Hyoji; Choi, Hoyun; Lee, Suk Kyeong

    2016-02-01

    Epstein-Barr virus (EBV) is a human gammaherpesvirus associated with a variety of tumor types. EBV can establish latency or undergo lytic replication in host cells. In general, EBV remains latent in tumors and expresses a limited repertoire of latent proteins to avoid host immune surveillance. When the lytic cycle is triggered by some as-yet-unknown form of stimulation, lytic gene expression and progeny virus production commence. Thus far, the exact mechanism of EBV latency maintenance and the in vivo triggering signal for lytic induction have yet to be elucidated. Previously, we have shown that the EBV microRNA miR-BART20-5p directly targets the immediate early genes BRLF1 and BZLF1 as well as Bcl-2-associated death promoter (BAD) in EBV-associated gastric carcinoma. In this study, we found that both mRNA and protein levels of BRLF1 and BZLF1 were suppressed in cells following BAD knockdown and increased after BAD overexpression. Progeny virus production was also downregulated by specific knockdown of BAD. Our results demonstrated that caspase-3-dependent apoptosis is a prerequisite for BAD-mediated EBV lytic cycle induction. Therefore, our data suggest that miR-BART20-5p plays an important role in latency maintenance and tumor persistence of EBV-associated gastric carcinoma by inhibiting BAD-mediated caspase-3-dependent apoptosis, which would trigger immediate early gene expression. EBV has an ability to remain latent in host cells, including EBV-associated tumor cells hiding from immune surveillance. However, the exact molecular mechanisms of EBV latency maintenance remain poorly understood. Here, we demonstrated that miR-BART20-5p inhibited the expression of EBV immediate early genes indirectly, by suppressing BAD-induced caspase-3-dependent apoptosis, in addition to directly, as we previously reported. Our study suggests that EBV-associated tumor cells might endure apoptotic stress to some extent and remain latent with the aid of miR-BART20-5p. Blocking the

  9. Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.

    Science.gov (United States)

    Hwang, J K; Erkhembaatar, M; Gu, D R; Lee, S H; Lee, C H; Shin, D M; Lee, Y R; Kim, M S

    2014-07-01

    Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+) channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably, after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis. © International & American Associations for Dental Research.

  10. Histone dosage regulates DNA damage sensitivity in a checkpoint-independent manner by the homologous recombination pathway

    Science.gov (United States)

    Liang, Dun; Burkhart, Sarah Lyn; Singh, Rakesh Kumar; Kabbaj, Marie-Helene Miquel; Gunjan, Akash

    2012-01-01

    In eukaryotes, multiple genes encode histone proteins that package genomic deoxyribonucleic acid (DNA) and regulate its accessibility. Because of their positive charge, ‘free’ (non-chromatin associated) histones can bind non-specifically to the negatively charged DNA and affect its metabolism, including DNA repair. We have investigated the effect of altering histone dosage on DNA repair in budding yeast. An increase in histone gene dosage resulted in enhanced DNA damage sensitivity, whereas deletion of a H3–H4 gene pair resulted in reduced levels of free H3 and H4 concomitant with resistance to DNA damaging agents, even in mutants defective in the DNA damage checkpoint. Studies involving the repair of a HO endonuclease-mediated DNA double-strand break (DSB) at the MAT locus show enhanced repair efficiency by the homologous recombination (HR) pathway on a reduction in histone dosage. Cells with reduced histone dosage experience greater histone loss around a DSB, whereas the recruitment of HR factors is concomitantly enhanced. Further, free histones compete with the HR machinery for binding to DNA and associate with certain HR factors, potentially interfering with HR-mediated repair. Our findings may have important implications for DNA repair, genomic stability, carcinogenesis and aging in human cells that have dozens of histone genes. PMID:22850743

  11. Sodium methyldithiocarbamate inhibits MAP kinase activation through toll-like receptor 4, alters cytokine production by mouse peritoneal macrophages, and suppresses innate immunity.

    Science.gov (United States)

    Pruett, Stephen B; Zheng, Qiang; Schwab, Carlton; Fan, Ruping

    2005-09-01

    Sodium methyldithiocarbamate (SMD; trade name, Metam Sodium) is an abundantly used soil fumigant that can cause adverse health effects in humans, including some immunological manifestations. The mechanisms by which SMD acts, and its targets within the immune system are not fully understood. Initial experiments demonstrated that SMD administered by oral gavage substantially decreased IL-12 production and increased IL-10 production induced by lipopolysaccharide in mice. The present study was conducted to further characterize these effects and to evaluate our working hypothesis that the mechanism for these effects involves alteration in signaling through toll-like receptor 4 and that this would suppress innate immunity to infection. SMD decreased the activation of MAP kinases and AP-1 but not NF-kappaB in peritoneal macrophages. The expression of mRNA for IL-1alpha, IL-1beta, IL-18, IFN-gamma, IL-12 p35, IL-12 p40, and macrophage migration inhibitory factor (MIF) was inhibited by SMD, whereas mRNA for IL-10 was increased. SMD increased the IL-10 concentration in the peritoneal cavity and serum and decreased the concentration of IL-12 p40 in the serum, peritoneal cavity, and intracellularly in peritoneal cells (which are >80% macrophages). Similar effects on LPS-induced cytokine production were observed following dermal administration of SMD. The major breakdown product of SMD, methylisothiocyanate (MITC), caused similar effects on cytokine production at dosages as low as 17 mg/kg, a dosage relevant to human exposure levels associated with agricultural use of SMD. Treatment of mice with SMD decreased survival following challenge with non-pathogenic Escherichia coli within 24-48 h, demonstrating suppression of innate immunity.

  12. REMINDER - Extension/suppression of allowance for dependent child

    CERN Multimedia

    Human Resources Department

    2005-01-01

    Members of the personnel with dependent children aged 18 or above (or reaching 18 during the 2005/2006 school year) have received a QUESTIONNAIRE in July. If this questionnaire has not been completed and returned yet, they are requested to do so WITHOUT DELAY. (The deadline was 9 September.) Human Resources Department Tel. 72862

  13. Effect of lead acetate administered orally at different dosage levels ...

    African Journals Online (AJOL)

    The project was conducted to evaluate the effect of lead administered as lead acetate at different dosage levels via drinking water in broiler chicks. Thirty-five healthy chicks were divided into seven groups (five chicks each) and one group was kept as un-medicated control. Groups A, B, C, D, E and F were medicated with ...

  14. Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery.

    Science.gov (United States)

    Battu, Sunil Kumar; Repka, Michael A; Maddineni, Sindhuri; Chittiboyina, Amar G; Avery, Mitchell A; Majumdar, Soumyajit

    2010-09-01

    The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a first step towards solution dosage form development. The parameters such as log P value were determined experimentally and compared with predicted values. The pH-dependent aqueous solubility and stability were investigated following standard protocols at 25°C and 37°C. Drug solubility enhancement was attempted utilizing both surfactants and cyclodextrins (CDs), and the drug/CD complexation was studied employing various techniques such as differential scanning calorimetry, Fourier transform infrared, nuclear magnetic resonance, and scanning electron microscopy. The experimental log P value suggested that the compound is fairly hydrophilic. Berberine chloride was found to be very stable up to 6 months at all pH and temperature conditions tested. Aqueous solubility of the drug was temperature dependent and exhibited highest solubility of 4.05 ± 0.09 mM in phosphate buffer (pH 7.0) at 25°C, demonstrating the effect of buffer salts on drug solubility. Decreased drug solubility was observed with increasing concentrations of ionic surfactants such as sodium lauryl sulfate and cetyl trimethyl ammonium bromide. Phase solubility studies demonstrated the formation of berberine chloride-HPβCD inclusion complex with 1:1 stoichiometry, and the aqueous solubility of the drug improved almost 4.5-fold in the presence of 20% HPβCD. The complexation efficiency values indicated that the drug has at least threefold greater affinity for hydroxypropyl-β-CD compared to randomly methylated-β-CD. The characterization techniques confirmed inclusion complex formation between berberine chloride and HPβCD and demonstrated the feasibility of developing an oral solution dosage form of the drug.

  15. Untangling the Contributions of Sex-Specific Gene Regulation and X-Chromosome Dosage to Sex-Biased Gene Expression in Caenorhabditis elegans

    Science.gov (United States)

    Kramer, Maxwell; Rao, Prashant; Ercan, Sevinc

    2016-01-01

    Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal’s sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in Caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function. PMID:27356611

  16. When and how should we teach the basic concepts of radiation beam dosage

    International Nuclear Information System (INIS)

    Brewin, T.B.

    1977-01-01

    The difficulty that many trainees, including those medically qualified, have in achieving a sound working grasp of certain basic principles of radiation beam dosage is often underestimated. Since any failure of understanding may seriously impair the efficiency of the team treating the patient, the discussion of these problems (and especially the monitoring of the results of such discussion by means of oral and written tests) deserves a high priority. Contrary to traditional practice, there would seem to be no good reason why teaching of radiation beam dosage, and the effect on dose-rate of changes in the treatment distance or in the amount of scattered radiation, should not begin in the very first week of training and be immediately integrated with discussion of the dose-rate information available at every radiotherapy unit when the patient is treated. A preliminary course of physics lectures does not usually make the understanding of these principles any easier and can be done either concurrently or later. For many radiotherapy trainees and for many doctors in other fields, comparison with drug dosage and with the brightness and scatter of ordinary light beams, avoiding technical terms so far as possible, may achieve a better initial understanding of basic principles than is achieved by mathematical equations and theoretical physics. (author)

  17. When and how should we teach the basic concepts of radiation beam dosage

    Energy Technology Data Exchange (ETDEWEB)

    Brewin, T B [Institute of Radiotherapeutics and Oncology, Glasgow (UK)

    1977-06-01

    The difficulty that many trainees, including those medically qualified, have in achieving a sound working grasp of certain basic principles of radiation beam dosage is often underestimated. Since any failure of understanding may seriously impair the efficiency of the team treating the patient, the discussion of these problems (and especially the monitoring of the results of such discussion by means of oral and written tests) deserves a high priority. Contrary to traditional practice, there would seem to be no good reason why teaching of radiation beam dosage, and the effect on dose-rate of changes in the treatment distance or in the amount of scattered radiation, should not begin in the very first week of training and be immediately integrated with discussion of the dose-rate information available at every radiotherapy unit when the patient is treated. A preliminary course of physics lectures does not usually make the understanding of these principles any easier and can be done either concurrently or later. For many radiotherapy trainees and for many doctors in other fields, comparison with drug dosage and with the brightness and scatter of ordinary light beams, avoiding technical terms so far as possible, may achieve a better initial understanding of basic principles than is achieved by mathematical equations and theoretical physics.

  18. Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation.

    Directory of Open Access Journals (Sweden)

    Guray Kuzu

    2016-07-01

    Full Text Available Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression.

  19. Deficient Suppression of Default Mode Regions during Working Memory in Individuals with Early Psychosis and at Clinical High-Risk for Psychosis.

    Science.gov (United States)

    Fryer, Susanna L; Woods, Scott W; Kiehl, Kent A; Calhoun, Vince D; Pearlson, Godfrey D; Roach, Brian J; Ford, Judith M; Srihari, Vinod H; McGlashan, Thomas H; Mathalon, Daniel H

    2013-01-01

    The default mode network (DMN) is a set of brain regions typically activated at rest and suppressed during extrinsic cognition. Schizophrenia has been associated with deficient DMN suppression, though the extent to which DMN dysfunction predates psychosis onset is unclear. This study examined DMN suppression during working memory (WM) performance in youth at clinical high-risk (CHR) for psychosis, early schizophrenia (ESZ) patients, and healthy controls (HC). We hypothesized that the DMN would show load-dependent suppression during WM retrieval in HC but not in ESZ, with CHR participants showing an intermediate pattern. fMRI data were collected from CHR (n = 32), ESZ (n = 22), and HC (n = 54) participants, ages 12-30. DMN regions were defined via seed-based connectivity analysis of resting-state fMRI data from an independent HC sample. Load-dependent deactivations of these DMN regions in response to WM probes were interrogated. Healthy controls showed linear load-dependent increases in DMN deactivation. Significant Group-by-Load interactions were observed in DMN regions including medial prefrontal and lateral posterior parietal cortices. Group-by-Load effects in posterior DMN nodes resulted from less suppression at higher WM loads in ESZ relative to HC, with CHR differing from neither group. In medial prefrontal cortex, suppression of activity at higher WM loads was significantly diminished in both CHR and ESZ groups, relative to HC. In addition, investigation of dorsolateral prefrontal cortex (DLPFC) activations revealed that ESZ activated right DLPFC significantly more than HC, with CHR differing from neither group. While HC showed WM load-dependent modulation of DMN suppression, CHR individuals had deficient higher-load DMN suppression that was similar to, but less pronounced than, the distributed suppression deficits evident in ESZ patients. These results suggest that DMN dysregulation associated with schizophrenia predates psychosis onset.

  20. Spectrophotometric methods for the determination of benazepril hydrochloride in its single and multi-component dosage forms.

    Science.gov (United States)

    El-Yazbi, F A; Abdine, H H; Shaalan, R A

    1999-06-01

    Three sensitive and accurate methods are presented for the determination of benazepril in its dosage forms. The first method uses derivative spectrophotometry to resolve the interference due to formulation matrix. The second method depends on the color formed by the reaction of the drug with bromocresol green (BCG). The third one utilizes the reaction of benazepril, after alkaline hydrolysis, with 3-methylbenzothialozone (MBTH) hydrazone where the produced color is measured at 593 nm. The latter method was extended to develop a stability-indicating method for this drug. Moreover, the derivative method was applied for the determination of benazepril in its combination with hydrochlorothiazide. The proposed methods were applied for the analysis of benazepril in the pure form and in tablets. The coefficient of variation was less than 2%.

  1. Endoglin-mediated suppression of prostate cancer invasion is regulated by activin and bone morphogenetic protein type II receptors.

    Directory of Open Access Journals (Sweden)

    Michael J Breen

    Full Text Available Mortality from prostate cancer (PCa is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor β (TGFβ superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon the type I TGFβ receptor, activin receptor-like kinase 2 (ALK2, and the downstream effector, Smad1. In this study we demonstrate for the first time that two type II TGFβ receptors are required for endoglin-mediated suppression of invasion: activin A receptor type IIA (ActRIIA and bone morphogenetic protein receptor type II (BMPRII. Downstream signaling through these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1 activation in a kinase-dependent manner, and this is required for suppression of invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting Smad1 signaling through its kinase domain but suppressing it through its cytoplasmic tail. BMPRII's Smad1-regulatory effects are dependent upon its expression level. Further, its ability to suppress invasion is independent of either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII physically interact, and that each also interacts with endoglin. The current findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin-mediated suppression of human PCa cell invasion, that they have differential effects on Smad1 signaling, that they make separate contributions to regulation of invasion, and that they functionally and physically interact.

  2. General lack of global dosage compensation in ZZ/ZW systems? Broadening the perspective with RNA-seq

    Directory of Open Access Journals (Sweden)

    Wolf Jochen BW

    2011-02-01

    Full Text Available Abstract Background Species with heteromorphic sex chromosomes face the challenge of large-scale imbalance in gene dose. Microarray-based studies in several independent male heterogametic XX/XY systems suggest that dosage compensation mechanisms are in place to mitigate the detrimental effects of gene dose differences. However, recent genomic research on female heterogametic ZZ/ZW systems has generated surprising results. In two bird species and one lepidopteran no evidence for a global dosage compensating mechanism has been found. The recent advent of massively parallel RNA sequencing now opens up the possibility to gauge the generality of this observation with a broader phylogenetic sampling. It further allows assessing the validity of microarray-based inference on dosage compensation with a novel technology. Results We here expemplify this approach using massively parallel sequencing on barcoded individuals of a bird species, the European crow (Corvus corone, where previously no genetic resources were available. Testing for Z-linkage with quantitative PCR (qPCR, we first establish that orthology with distantly related species (chicken, zebra finch can be used as a good predictor for chromosomal affiliation of a gene. We then use a digital measure of gene expression (RNA-seq on brain transcriptome and confirm a global lack of dosage compensation on the Z chromosome. RNA-seq estimates of male-to-female (m:f expression difference on the Z compare well to previous microarray-based estimates in birds and lepidopterans. The data further lends support that an up-regulation of female Z-linked genes conveys partial compensation and suggest a relationship between sex-bias and absolute expression level of a gene. Correlation of sex-biased gene expression on the Z chromosome across all three bird species further suggests that the degree of compensation has been partly conserved across 100 million years of avian evolution. Conclusions This work

  3. Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway.

    Directory of Open Access Journals (Sweden)

    Ruey-Hwang Chou

    Full Text Available Fisetin (3,3',4',7-tetrahydroxyflavone, a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.

  4. Fisetin Inhibits Migration and Invasion of Human Cervical Cancer Cells by Down-Regulating Urokinase Plasminogen Activator Expression through Suppressing the p38 MAPK-Dependent NF-κB Signaling Pathway

    Science.gov (United States)

    Chou, Ruey-Hwang; Hsieh, Shu-Ching; Yu, Yung-Luen; Huang, Min-Hsien; Huang, Yi-Chang; Hsieh, Yi-Hsien

    2013-01-01

    Fisetin (3,3’,4’,7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion. PMID:23940799

  5. Suppression of β3-integrin in mice triggers a neuropilin-1-dependent change in focal adhesion remodelling that can be targeted to block pathological angiogenesis

    Directory of Open Access Journals (Sweden)

    Tim S. Ellison

    2015-09-01

    Full Text Available Anti-angiogenic treatments against αvβ3-integrin fail to block tumour growth in the long term, which suggests that the tumour vasculature escapes from angiogenesis inhibition through αvβ3-integrin-independent mechanisms. Here, we show that suppression of β3-integrin in mice leads to the activation of a neuropilin-1 (NRP1-dependent cell migration pathway in endothelial cells via a mechanism that depends on NRP1's mobilisation away from mature focal adhesions following VEGF-stimulation. The simultaneous genetic targeting of both molecules significantly impairs paxillin-1 activation and focal adhesion remodelling in endothelial cells, and therefore inhibits tumour angiogenesis and the growth of already established tumours. These findings provide a firm foundation for testing drugs against these molecules in combination to treat patients with advanced cancers.

  6. 17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression.

    Science.gov (United States)

    Xiao, Y; Guan, J

    2015-01-01

    Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti-tumor activity in hematologic malignancies. However, Flavopiridol-induced protective autophagy may lead to drug resistance. Here we found that Hsp90 inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol by suppressing flavopiridol-triggered protective autophagy. The suppressing effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and growth suppression in MCL cells. Our study may provide some insights into CDKI -targeted chemotherapies.

  7. Analysis of the dosage compensation of a specific transcript in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Breen, T.R.

    1985-01-01

    The basic tenet of dosage compensation is that males, which normally have one X-chromosome that contains half the amount of DNA as the two X-chromosomes in females, produce a relatively equivalent amount of X-encoded gene products compared to females. Quantitative analyses were performed to ascertain the amount of transcripts synthesized from the X-linked salivary gland secretion protein gene, Sgs-4, in larval third instar males and females which had a variety of genetic backgrounds. Two types of analyses were performed. In one, RNA from male and female late third instar salivary glands was isolated and quantitatively blotted to replica nitrocellulose filters. The replicas were hybridized with 32 P-labeled probes specific for either Sgs-4 or Sgs-3 RNA. The radioactive hybrids were quantitated by scintillation counting. In the other, male and female third instar salivary glands were incubated for 12.5 minutes with 3 H-uridine. The labelled, nascent RNAs were hybridized to dot blots of Sgs-4 and Sgs-3 DNA, and were scintillation counted. 3 H-uridine incorporation analysis showed that male Sgs-4 genes were transcribed at twice the rate of the female genes. These findings indicated that steady-state Sgs-4 RNA levels directly reflect the rate of their transcription. These results are important in that they demonstrate that dosage compensation operates at the level of the rate of transcription of a specific gene. They also dissolve ambiguities associated with results obtained in past dosage compensation experiments

  8. Meta-analysis : High-dosage vitamin E supplementation may increase all-cause mortality

    NARCIS (Netherlands)

    Miller, ER; Pastor-Barriuso, R; Dalal, D; Riemersma, RA; Appel, LJ; Guallar, E

    2005-01-01

    Background: Experimental models and observational studies suggest that vitamin E supplementation may prevent cardiovascular disease and cancer. However, several trials of high-dosage vitamin E supplementation showed non-statistically significant increases in total mortality. Purpose: To perform a

  9. THE INFLUENCE OF CALCIUM HYPOCHLORITE DOSAGE ADJUSTMENT ON TAPIOCA WASTEWATER PRE-CHLORINATION TOWARD EFFICIENCY OF ACTIVATED SLUDGE TREATMENT

    Directory of Open Access Journals (Sweden)

    Happy Mulyani

    2016-11-01

    Full Text Available The objectives of this research are to study about influence of calcium hypochlorite dosage adjustment on tapioca wastewater chlorination toward efficiency of activated sludge treatment especially at MLVSS profile and percentage of COD removal. This research mainly divided into pre-chlorination and activated sludge treatment. Pre-chlorination taken place for 60 minutes at pH 8. The variation of calcium hypochlorite dosages which used are 58, 59, and 60 mg/L. Pre-chlorination effluent with no free chlorine residual then becomes activated sludge treatment influent. Sampling has done each aeration time interval 0, 2, 4, and 6 hour for analysis of COD and MLVSS content. Research result generally shows that addition of aeration time for each variation of calcium hypochlorite dosage will increase MLVSS and decrease COD content. Smallest value of COD effluent could achieved in the activated sludge treatment with calcium hipochlorite dosage 60 mg/L addition at influent during 4 hours aeration time. Addition of 58 mg/l calcium hypochlorite results highest MLVSS and percentage of COD removal.

  10. Clinical efficacy of dexmedetomidine in the diminution of fentanyl dosage in pediatric cardiac surgery.

    Science.gov (United States)

    Sun, Yingying; Ye, Hongwu; Xia, Yin; Li, Yuanhai; Yuan, Xianren; Wang, Xing

    2017-06-01

    This study aims to explore the clinical efficacy of dexmedetomidine (DEX) in the diminution of fentanyl dosage in pediatric cardiac surgery based on some clinical and biochemical parameters. Fifty pediatric patients (American Society of Anesthesiologists II), 1-6 years old, were randomly allocated into two groups: group F (control group), in which patients received normal saline and high dosage of fentanyl (30 μg/kg), and group D, in which patients were given DEX and low dosage of fentanyl (15 μg/kg). Some hemodynamic and clinical parameters of the two groups were recorded. Furthermore, stress hormone (serum cortisol, norepinephrine, blood glucose) levels and cytokine (interleukin 6, tumor necrosis factor alpha) levels in the two groups were compared with each other. Stress hormone levels, cytokine levels, hemodynamic parameters and the consumption of sevoflurane did not differ between the two groups. Meanwhile, the extubation time was significantly shorter in Group D than F (Pfentanyl supplemented with DEX almost had the same anesthesia effects and inflammation extent compared with high dose of fentanyl, which suggested that infusion DEX might decrease fentanyl consumption in pediatric cardiac surgery.

  11. Variation in plant defense suppresses herbivore performance

    Science.gov (United States)

    Pearse, Ian; Paul, Ryan; Ode, Paul J.

    2018-01-01

    Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory. However, it is still unknown how defense variability translates into herbivore suppression. Nonlinear averaging and constraints in physiological tracking (also more generally called time-dependent effects) are the two mechanisms by which defense variability might impact herbivores. We conducted a set of experiments manipulating the mean and variability of a plant defense, showing that defense variability does suppress herbivore performance and that it does so through physiological tracking effects that cannot be explained by nonlinear averaging. While nonlinear averaging predicted higher or the same herbivore performance on a variable defense than on an invariable defense, we show that variability actually decreased herbivore performance and population growth rate. Defense variability reduces herbivore performance in a way that is more than the average of its parts. This is consistent with constraints in physiological matching of detoxification systems for herbivores experiencing variable toxin levels in their diet and represents a more generalizable way of understanding the impacts of variability on herbivory. Increasing defense variability in croplands at a scale encountered by individual herbivores can suppress herbivory, even if that is not anticipated by nonlinear averaging.

  12. Suppression of spatio-temporal chaos in simple models of re-entrant fibrillations

    Energy Technology Data Exchange (ETDEWEB)

    Vysotsky, Semion A [Student, Faculty of Physics, M.V.Lomonosov Moscow State Universitry, Leninskie Gory, 119992 Moscow (Russian Federation); Cheremin, Ruslan V [Research Scientist, Faculty of Physics, M.V.Lomonosov Moscow State Universitry, Leninskie Gory, 119992 Moscow (Russian Federation); Loskutov, Alexander [Professor, Faculty of Physics, M.V.Lomonosov Moscow State Universitry, Leninskie Gory, 119992 Moscow (Russian Federation)

    2005-01-01

    On the basis of the FitzHugh-Nagumo-type model we investigate the possibility of suppression of the spiral wave turbulence by weak pacemaker excitations. We consider different ways of media stabilization and study the dependence of the suppression efficiency on the excitation shape and the media parameters. Also, we analyze the frequency of target waves in the unperturbed media as a function of the external force frequency. Applications of the obtained results to cardiac rhythm pathologies are considered.

  13. Suppression of contour perception by band-limited noise and its relation to nonclassical receptive field inhibition

    NARCIS (Netherlands)

    Petkov, Nicolai; Westenberg, Michel A.

    Band-spectrum noise has been shown to suppress the visual perception of printed letters. The suppression exhibits a specific dependence on the spatial frequency of the noise, and the frequency domain of most effective inhibition has been related to the size of the letters. In this paper, we address

  14. p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes

    Science.gov (United States)

    Anur, Praveen; Yates, Jane; Garbati, Michael R.; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E.; Tyner, Jeffrey W.; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo

    2012-01-01

    Fanconi anemia, complementation group C (FANCC)–deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist–stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)–deficient macrophages containing an NF-κB/AP-1–responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK–dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation. PMID:22234699

  15. p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes.

    Science.gov (United States)

    Anur, Praveen; Yates, Jane; Garbati, Michael R; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E; Tyner, Jeffrey W; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo; Bagby, Grover C

    2012-03-01

    Fanconi anemia, complementation group C (FANCC)-deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist-stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)-deficient macrophages containing an NF-κB/AP-1-responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK-dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation.

  16. Sedative and mechanical antinociceptive effects of four dosages of romifidine administered intravenously to donkeys.

    Science.gov (United States)

    Lizarraga, Ignacio; Castillo-Alcala, Fernanda; Robinson, Lauren S

    2017-06-01

    Although romifidine is commonly used to provide sedation and analgesia for the facilitation of clinical procedures in donkeys, limited scientific information is available for this drug in this species. This randomized, controlled, crossover, Latin-square, blinded study compared the sedative and antinociceptive effects of four dosages of romifidine (40, 60, 80, and 100μg/kg IV; R40, R60, R80, and R100, respectively), acepromazine (0.1mg/kg IV; ACE) and saline (0.9%, 5mL IV) by assigning sedation scores (SS) and measuring head heights above ground (HHAG) and mechanical nociceptive thresholds (MNT) in donkeys. Areas under the curve (AUC) from 0 to 30, 30-60, 60-120, and 120-180min after administration were computed for SS, HHAG, and MNT and compared among treatments. Romifidine and ACE, but not saline, induced clinical signs of sedation. SS-AUC 0-30 for R60, R80 and R100, and SS-AUC 30-60 for R100 were higher than corresponding values for saline. HHAG-AUC 30-60 for R40 and R80, and HHAG-AUC 60-120 for R40, R60, R80 and R100 were smaller than for saline. HHAG-AUC 60-120 for R100 were also smaller than those for ACE. Romifidine, but not saline or ACE, increased MNT. MNT-AUC 0-30 and MNT-AUC 30-60 for R40, R60, R80 and R100, and MNT-AUC 60-120 for R80 and R100 were higher than corresponding values for saline and ACE. MNT-AUC 60-120 for R100 were higher than for all other romifidine treatments. In donkeys, the degree of sedation was similar for the four dosages of romifidine, but antinociception was dose-dependent. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Calculation of Fire Severity Factors and Fire Non-Suppression Probabilities For A DOE Facility Fire PRA

    International Nuclear Information System (INIS)

    Elicson, Tom; Harwood, Bentley; Lucek, Heather; Bouchard, Jim

    2011-01-01

    Over a 12 month period, a fire PRA was developed for a DOE facility using the NUREG/CR-6850 EPRI/NRC fire PRA methodology. The fire PRA modeling included calculation of fire severity factors (SFs) and fire non-suppression probabilities (PNS) for each safe shutdown (SSD) component considered in the fire PRA model. The SFs were developed by performing detailed fire modeling through a combination of CFAST fire zone model calculations and Latin Hypercube Sampling (LHS). Component damage times and automatic fire suppression system actuation times calculated in the CFAST LHS analyses were then input to a time-dependent model of fire non-suppression probability. The fire non-suppression probability model is based on the modeling approach outlined in NUREG/CR-6850 and is supplemented with plant specific data. This paper presents the methodology used in the DOE facility fire PRA for modeling fire-induced SSD component failures and includes discussions of modeling techniques for: Development of time-dependent fire heat release rate profiles (required as input to CFAST), Calculation of fire severity factors based on CFAST detailed fire modeling, and Calculation of fire non-suppression probabilities.

  18. Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release.

    Directory of Open Access Journals (Sweden)

    Varun K Gupta

    2016-09-01

    Full Text Available Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ, increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse.

  19. Evidence that shock-induced immune suppression is mediated by adrenal hormones and peripheral beta-adrenergic receptors.

    Science.gov (United States)

    Cunnick, J E; Lysle, D T; Kucinski, B J; Rabin, B S

    1990-07-01

    Our previous work has demonstrated that presentations of mild foot-shock to Lewis rats induces a suppression of splenic and peripheral blood lymphocyte responses to nonspecific T-cell mitogens. The present study demonstrated that adrenalectomy prevented the shock-induced suppression of the mitogenic response of peripheral blood T-cells but did not attenuate the suppression of splenic T-cells. Conversely, the beta-adrenergic receptor antagonists, propranolol and nadolol, attenuated the shock-induced suppression of splenic T-cells in a dose-dependent manner but did not attenuate suppression of the blood mitogen response. These data indicate that distinct mechanisms mediate the shock-induced suppression of T-cell responsiveness to mitogens in the spleen and the peripheral blood. The results indicate that the peripheral release of catecholamines is responsible for splenic immune suppression and that adrenal hormones, which do not interact with beta-adrenergic receptors, are responsible for shock-induced suppression of blood mitogenic responses.

  20. Sativex Associated With Behavioral-Relapse Prevention Strategy as Treatment for Cannabis Dependence: A Case Series.

    Science.gov (United States)

    Trigo, Jose M; Soliman, Alexandra; Staios, Gregory; Quilty, Lena; Fischer, Benedikt; George, Tony P; Rehm, Jürgen; Selby, Peter; Barnes, Allan J; Huestis, Marilyn A; Le Foll, Bernard

    2016-01-01

    Cannabis is the most commonly used illicit drug; a substantial minority of users develop dependence. The current lack of pharmacological treatments for cannabis dependence warrants the use of novel approaches and further investigation of promising pharmacotherapy. In this case series, we assessed the use of self-titrated dosages of Sativex (1:1, Δ-tetrahydrocannabinol [THC]/cannabidiol [CBD] combination) and motivational enhancement therapy and cognitive behavioral therapy (MET/CBT) for the treatment of cannabis dependence among 5 treatment-seeking community-recruited cannabis-dependent subjects. Participants underwent a 3-month open-label self-titration phase with Sativex (up to 113.4 of THC/105 mg of CBD) and weekly MET/CBT, with a 3-month follow-up. Sativex was well-tolerated by all participants (average dosage 77.5 THC/71.7 mg CBD). The combination of Sativex and MET/CBT reduced the amount of cannabis use and progressively reduced craving and withdrawal scores. THC/CBD metabolite concentration indicated reduced cannabis use and compliance with medication. In summary, this pilot study found that with Sativex in combination with MET/CBT reduced cannabis use while preventing increases in craving and withdrawal in the 4 participants completing the study. Further systematic exploration of Sativex as a pharmacological treatment option for cannabis dependence should be performed.

  1. Suppressed Belief

    Directory of Open Access Journals (Sweden)

    Komarine Romdenh-Romluc

    2009-12-01

    Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

  2. Consequences of stereotype suppression and internal suppression motivation : A self-regulation approach

    NARCIS (Netherlands)

    Gordijn, Ernestine H; Hindriks, Inge; Koomen, W; Dijksterhuis, Ap; van Knipppenberg, A.

    The present research studied the effects of suppression of stereotypes on subsequent stereotyping. Moreover, the moderating influence of motivation to suppress stereotypes was examined. The first three experiments showed that suppression of stereotypes leads to the experience of engaging in

  3. Discrete element method (DEM) simulations of stratified sampling during solid dosage form manufacturing.

    Science.gov (United States)

    Hancock, Bruno C; Ketterhagen, William R

    2011-10-14

    Discrete element model (DEM) simulations of the discharge of powders from hoppers under gravity were analyzed to provide estimates of dosage form content uniformity during the manufacture of solid dosage forms (tablets and capsules). For a system that exhibits moderate segregation the effects of sample size, number, and location within the batch were determined. The various sampling approaches were compared to current best-practices for sampling described in the Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) guidelines. Sampling uniformly across the discharge process gave the most accurate results with respect to identifying segregation trends. Sigmoidal sampling (as recommended in the PQRI BUWG guidelines) tended to overestimate potential segregation issues, whereas truncated sampling (common in industrial practice) tended to underestimate them. The size of the sample had a major effect on the absolute potency RSD. The number of sampling locations (10 vs. 20) had very little effect on the trends in the data, and the number of samples analyzed at each location (1 vs. 3 vs. 7) had only a small effect for the sampling conditions examined. The results of this work provide greater understanding of the effect of different sampling approaches on the measured content uniformity of real dosage forms, and can help to guide the choice of appropriate sampling protocols. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology.

    Science.gov (United States)

    Mohammed, Noorullah Naqvi; Majumdar, Soumyajit; Singh, Abhilasha; Deng, Weibin; Murthy, Narasimha S; Pinto, Elanor; Tewari, Divya; Durig, Thomas; Repka, Michael A

    2012-12-01

    The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

  5. Application of DBNPA dosage for biofouling control in spiral wound membrane systems

    KAUST Repository

    Siddiqui, Amber; Pinel, I.; Prest, E.I.; Bucs, Szilard; van Loosdrecht, M.C.M.; Kruithof, J.C.; Vrouwenvelder, Johannes S.

    2017-01-01

    in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can

  6. A multicenter study of the effect of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis.

    Science.gov (United States)

    Fritsch, Dale A; Allen, Timothy A; Dodd, Chadwick E; Jewell, Dennis E; Sixby, Kristin A; Leventhal, Phillip S; Brejda, John; Hahn, Kevin A

    2010-03-01

    To determine the effects of feeding a diet supplemented with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. Randomized, controlled, multisite clinical trial. 131 client-owned dogs with stable chronic osteoarthritis examined at 33 privately owned veterinary hospitals in the United States. In all dogs, the dosage of carprofen was standardized over a 3-week period to approximately 4.4 mg/kg/d (2 mg/lb/d), PO. Dogs were then randomly assigned to receive a food supplemented with fish oil omega-3 fatty acids or a control food with low omega-3 fatty acid content, and 3, 6, 9, and 12 weeks later, investigators made decisions regarding increasing or decreasing the carprofen dosage on the basis of investigator assessments of 5 clinical signs and owner assessments of 15 signs. Linear regression analysis indicated that over the 12-week study period, carprofen dosage decreased significantly faster among dogs fed the supplemented diet than among dogs fed the control diet. The distribution of changes in carprofen dosage for dogs in the control group was significantly different from the distribution of changes in carprofen dosage for dogs in the test group. Results suggested that in dogs with chronic osteoarthritis receiving carprofen because of signs of pain, feeding a diet supplemented with fish oil omega-3 fatty acids may allow for a reduction in carprofen dosage.

  7. Derivative spectrophotometric method for simultaneous determination of clindamycin phosphate and tretinoin in pharmaceutical dosage forms.

    Science.gov (United States)

    Barazandeh Tehrani, Maliheh; Namadchian, Melika; Fadaye Vatan, Sedigheh; Souri, Effat

    2013-04-10

    A derivative spectrophotometric method was proposed for the simultaneous determination of clindamycin and tretinoin in pharmaceutical dosage forms. The measurement was achieved using the first and second derivative signals of clindamycin at (1D) 251 nm and (2D) 239 nm and tretinoin at (1D) 364 nm and (2D) 387 nm.The proposed method showed excellent linearity at both first and second derivative order in the range of 60-1200 and 1.25-25 μg/ml for clindamycin phosphate and tretinoin respectively. The within-day and between-day precision and accuracy was in acceptable range (CVpharmaceutical dosage form.

  8. Activation of the ζ receptor 1 suppresses NMDA responses in rat retinal ganglion cells.

    Science.gov (United States)

    Zhang, X-J; Liu, L-L; Jiang, S-X; Zhong, Y-M; Yang, X-L

    2011-03-17

    The sigma receptor 1 (σR1) has been shown to modulate the activity of several voltage- and ligand-gated channels. Using patch-clamp techniques in rat retinal slice preparations, we demonstrated that activation of σR1 by SKF10047 (SKF) or PRE-084 suppressed N-methyl-D-aspartate (NMDA) receptor-mediated current responses from both ON and OFF type ganglion cells (GCs), dose-dependently, and the effect could be blocked by the σR1 antagonist BD1047 or the σR antagonist haloperidol. The suppression by SKF of NMDA currents was abolished with pre-incubation of the G protein inhibitor GDP-β-S or the Gi/o activator mastoparan. We further explored the intracellular signaling pathway responsible for the SKF-induced suppression of NMDA responses. Application of either cAMP/the PKA inhibitor Rp-cAMP or cGMP/the PKG inhibitor KT5823 did not change the SKF-induced effect, suggesting the involvement of neither cAMP/PKA nor cGMP/PKG pathway. In contrast, suppression of NMDA responses by SKF was abolished by internal infusion of the phosphatidylinostiol-specific phospholipase C (PLC) inhibitor U73122, but not by the phosphatidylcholine-PLC inhibitor D609. SKF-induced suppression of NMDA responses was dependent on intracellular Ca2+ concentration ([Ca2+]i), as evidenced by the fact that the effect was abolished when [Ca2+]i was buffered with 10 mM BAPTA. The SKF effect was blocked by xestospongin-C/heparin, IP3 receptor antagonists, but unchanged by ryanodine/caffeine, ryanodine receptor modulators. Furthermore, application of protein kinase C inhibitors Bis IV and Gö6976 eliminated the SKF effect. These results suggest that the suppression of NMDA responses of rat retinal GCs caused by the activation of σR1 may be mediated by a distinct [Ca2+]i-dependent PLC-PKC pathway. This effect of SKF could help ameliorate malfunction of GCs caused by excessive stimulation of NMDA receptors under pathological conditions. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights

  9. Intra-individual comparison of PET/CT with different body weight-adapted FDG dosage regimens

    International Nuclear Information System (INIS)

    Geismar, Jan H; Stolzmann, Paul; Sah, Bert-Ram; Burger, Irene A; Seifert, Burkhardt; Delso, Gaspar; Schulthess, Gustav K von; Veit-Haibach, Patrick; Husmann, Lars

    2015-01-01

    18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/ computed tomography (CT) imaging demands guidelines to safeguard sufficient image quality at low radiation exposure. Various FDG dose regimes have been investigated; however, body weight-adapted dose regimens and related image quality (IQ) have not yet been compared in the same patient. To investigate the relationship between FDG dosage and image quality in PET/CT in the same patient and determine prerequisites for low dosage scanning. This study included 61 patients undergoing a clinically indicated PET/CT imaging study and follow-up with a normal (NDS, 5 MBq/kg body weight [BW]) and low dosage scanning protocol (LDS, 4 MBq/kg BW), respectively, using a Discovery VCT64 scanner. Two blinded and independent readers randomly assessed IQ of PET using a 5-point Likert scale and signal-to-noise ratio (SNR) of the liver. Body mass index (BMI) was significantly lower at LDS (P = 0.021) and represented a significant predictor of SNR at both NDS (P < 0.001) and LDS (P = 0.005). NDS with a mean administered activity of 340 MBq resulted in significantly higher IQ (P < 0.001) and SNR as compared with LDS with a mean of 264 MBq (F-value = 23.5, P < 0.001, mixed model ANOVA adjusted for covariate BMI). Non-diagnostic IQ at LDS was associated with a BMI > 22 kg/m 2 . FDG dosage significantly predicts IQ and SNR in PET/CT imaging as demonstrated in the same patient with optimal IQ achieved at 5 MBq/kg BM. PET/CT imaging at 4 MBq/kg BW may only be recommended in patients with a BMI ≤ 22 kg/m 2 to maintain diagnostic IQ

  10. [Oral films as perspective dosage form].

    Science.gov (United States)

    Walicová, Veronika; Gajdziok, Jan

    Oral films, namely buccal mucoadhesive films and orodispersible films represent innovative formulations for administration of a wide range of drugs. Oral films show many advantageous properties and are intended for systemic drug delivery or for local treatment of the oral mucosa. In both cases, the film represents a thin layer, which could be intended to adhere to the oral mucosa by means of mucoadhesion; or to rapid dissolution and subsequent swallowing without the need of liquid intake, in the case of orodispersible films. Main constitutive excipients are film-forming polymers, which must in the case of mucoadhesive forms remain on the mucosa within the required time interval. Oral films are currently available on the pharmaceutical market and could compete with conventional oral dosage forms in the future. oral cavity oral films buccal mucoadhesive films orodispersible films film-forming polymers.

  11. Standardization of radioimmunoassay for dosage of angiotensin II (ang-II) and its methodological evaluation

    International Nuclear Information System (INIS)

    Mantovani, Milene; Mecawi, Andre S.; Elias, Lucila L.K.; Antunes-Rodrigues, Jose

    2011-01-01

    This paper standardizes the radioimmunoassay (RIA) for dosage of ANG-II of rats, after experimental conditions of saline hypertonic (2%), treating with losartan (antagonist of ANG-II), hydric privation, and acute hemorrhage (25%). After that, the plasmatic ANG-II was extracted for dosage of RIA, whose sensitiveness was of 1.95 pg/m L, with detection of 1.95 to 1000 pg/m L. The treatment with saline reduced the concentration of ANG-II, while the administration pf losartan, the hydric administration and the hemorrhage increase the values, related to the control group. Those results indicate variations in the plasmatic concentration of ANG-II according to the experimental protocols, validating the method for evaluation of activity renin-angiotensin

  12. Patient perception of methadone dose adequacy in methadone maintenance treatment: The role of perceived participation in dosage decisions.

    Science.gov (United States)

    Trujols, Joan; González-Saiz, Francisco; Manresa, María José; Alcaraz, Saul; Batlle, Francesca; Duran-Sindreu, Santiago; Pérez de Los Cobos, José

    2017-05-01

    In clinical practice, methadone maintenance treatment (MMT) entails tailoring the methadone dose to the patient's specific needs, thereby individualizing treatment. The aim of this study was to identify the independent factors that may significantly explain methadone dose adequacy from the patient's perspective. Secondary analysis of data collected in a treatment satisfaction survey carried out among a representative sample of MMT patients (n=122) from the region of La Rioja (Spain). As part of the original study protocol, participants completed a comprehensive battery to assess satisfaction with MMT, psychological distress, opinion of methadone as a medication, participation in dosage decisions, and perception of dose adequacy. Multivariate binary logistic regression showed that the only variable independently associated with the likelihood of a patient perceiving methadone dose as inadequate was the variable perceived-participation in methadone dosage decisions (OR=0.538, 95% CI=0.349-0.828). Patient participation in methadone dosage decisions was predictive of perceived adequacy of methadone dose beyond the contribution of other socio-demographic, clinical, and MMT variables. Patient participation in methadone dosage decision-making is valuable for developing a genuinely patient-centred MMT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. 76 FR 16533 - Certain Other Dosage Form New Animal Drugs; Detomidine; Correction

    Science.gov (United States)

    2011-03-24

    .... FDA-2010-N-0002] Certain Other Dosage Form New Animal Drugs; Detomidine; Correction AGENCY: Food and... paragraph describing limitations to the approved conditions of use for detomidine hydrochloride oromucosal... conditions of use for detomidine hydrochloride oromucosal gel in horses. This correction is being made to...

  14. The influence of Aspergillus niger inoculum dosage on nutritive value and metabolizable energy of apu-apu meal (Pistia stratiotes L.) on broiler chicken

    Science.gov (United States)

    Gloria, J.; Tafsin, M.; Hanafi, N. D.; Daulay, A. H.

    2018-02-01

    Apu-apu lives at tropical and subtropical fresh waterways. The apu-apu meals ultization as feed still limited. The problem of ultization apu-apu meals as ingredients is a high crude fiber and need a treatment to decrease crude fiber. This study aim to find out the influence of Aspergillus niger inoculums dosage on apu-apu meal (Pistia stratiotes L.) on metabolizable energy on broiler chicken. This research used completely randomize design (CRD). The treatments consists of Aspergillus niger inoculum dosage (CFU/g) such as P0 (0), P1 (104 CFU/g), P2 (106 CFU/g), and P3 (108 CFU/g). The variable were observed : apparent metabolizable energy (AME), true metabolizable energy (TME), apparent metabolizable energy nitrogen corrected (AMEn) and true metabolizable energy nitrogen corrected (TMEn).The results showed that the dosage of Aspergillus niger increase nutritive value of Aspergillus niger. Dosage of Aspergillus niger also influence (P<0.05) metabolizable energy of apu-apu meals. Dosage 108 CFU/g had metabolizable energy significantly higher than other treatments. Conclusion of this research is the Aspergillus niger at the dosage 108 CFU/g increased nutritive value and metabolizable energy of apu-apu meal.

  15. Development of polymer film dosage forms of lidocaine for buccal administration. I. Penetration rate and release rate.

    Science.gov (United States)

    Okamoto, H; Taguchi, H; Iida, K; Danjo, K

    2001-12-13

    We examined the penetration rate of lidocaine (LC) through excised oral mucosa from hamster cheek pouch and the in vitro release rate of LC from film dosage forms with hydroxypropylcellulose (HPC) as a film base. Addition of glycyrrhizic acid (GL) to the HPC films increased the LC release rate almost GL-content-dependently, while an optimum GL content was observed for the LC penetration rate. No LC penetration was observed from an acidic aqueous solution (pH 3.4) of LC, suggesting only unionized LC can substantially penetrate through the mucosa. A significant relationship between the penetration rate of LC and the release rate of unionized LC was found, suggesting that the in vitro dissolution study is a useful tool to predict the penetration rate taking the unionized drug fraction into consideration.

  16. Effects of music on psychophysiological responses and opioid dosage in patients undergoing total knee replacement surgery.

    Science.gov (United States)

    Chen, Hsin-Ji; Chen, Tsung-Ying; Huang, Chiung-Yu; Hsieh, Yuan-Mei; Lai, Hui-Ling

    2015-10-01

    The present authors examined the effects of listening to music on psychophysiological parameters (blood pressure, heart rate, and respiratory rate) during preoperative and postoperative days and determined whether listening to music could lower pain intensity and opioid dosage during postoperative days in patients who underwent total knee replacements. This was a two group repeated measures design for 30 subjects aged 53-85 years who were scheduled for total knee replacement. Subjects were randomly assigned to either a music group or a control group. Psychophysiological parameters were obtained from patients' monitors. A visual analog scale was used to assess postoperative pain. Opioid dosage was recorded and converted to standardized units. Mann-Whitney U-test and generalized estimating equation analysis were used to compare groups. Respiratory rates while in the surgical waiting area were lower for the music group than for the control group (P = 0.02). There was no significant difference between these groups for blood pressure, heart rate, pain intensity, or opioid dosage. However, a within-group comparison showed that systolic blood pressure in the music group was significantly and consistently decreased during postoperative recovery (Wald = 9.21, P = 0.007). These results suggest that listening to music stabilized systolic blood pressure in patients during postoperative recovery. However, the effects of music on psychophysiological parameters, pain intensity, and opioid dosage in a surgical setting require further research. © 2015 The Authors. Japan Journal of Nursing Science © 2015 Japan Academy of Nursing Science.

  17. Normal mitogen-induced suppression of the interleukin-6 (IL-6) response and its deficiency in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Warrington, R.J.; Rutherford, W.J.

    1990-01-01

    A low-frequency suppressor-cell population in normal peripheral blood inhibits the B-cell CESS response to IL-6, following pokeweed mitogen stimulation. The suppression of IL-6 responsiveness is radiation sensitive, directed against CESS targets and not mediated by inhibition of IL-6 production, and associated with nonspecific cytotoxic activity against CESS targets. The generation of these cytolytic cells is also radiation sensitive. A correlation was found between PWM-induced cytotoxicity against CESS and the suppression of IL-6-dependent IgG production. But cytotoxicity toward CESS targets is not responsible for this suppression because IL-2 induces equivalent or greater nonspecific cytotoxicity against CESS in the total absence of suppression of CESS-derived IgG production and suppression is also induced by mitogen-activated PBL separated from CESS targets by a cell-impermeable membrane. This suppression was not mediated by TNF alpha/beta or IFN-gamma. In systemic lupus erythematosus, suppression of IL-6-dependent IgG production is impaired in patients with active disease (29.2 +/- 13.7%) compared to patients with inactive disease (70 +/- 19.5%) or normal controls (82.8 +/- 9.2%). There is also a defect in mitogen-induced nonspecific cytotoxicity in active SLE (specific lysis 15.1 +/- 3.5%, compared to 34 +/- 4% in normals). Pokeweed mitogen-activated PBL can therefore normally induce suppression of B-cell IL-6 responses and this response is deficient in lupus

  18. The effect of different dosages of caffeine on endurance performance time

    NARCIS (Netherlands)

    Pasman, W.J.; Baak, M.A. van; Jeukendrup, A.E.; Haan, A. de

    1995-01-01

    The effect of different dosages of caffeine (0 - 5 - 9 - 13 mg · kg body weight-1) on endurance performance was examined. Nine well-trained cyclists participated in this study (VO2max 65.1 + 2.6 ml · kg-1 · min-1). Caffeine capsules were administered in random order and double-blind. One hour after

  19. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

  20. Kefiran suppresses antigen-induced mast cell activation.

    Science.gov (United States)

    Furuno, Tadahide; Nakanishi, Mamoru

    2012-01-01

    Kefir is a traditional fermented milk beverage produced by kefir grains in the Caucasian countries. Kefiran produced by Lactobacillus kefiranofaciens in kefir grains is an exopolysaccharide having a repeating structure with glucose and galactose residues in the chain sequence and has been suggested to exert many health-promoting effects such as immunomodulatory, hypotensive, hypocholesterolemic activities. Here we investigated the effects of kefiran on mast cell activation induced by antigen. Pretreatment with kefiran significantly inhibited antigen-induced Ca(2+) mobilization, degranulation, and tumor necrosis factor-α production in bone marrow-derived mast cells (BMMCs) in a dose-dependent manner. The phosphorylation of Akt, glycogen synthase kinase 3β, and extracellular signal-regulated kinases (ERKs) after antigen stimulation was also suppressed by pretreatment of BMMCs with kefiran. These findings indicate that kefiran suppresses mast cell degranulation and cytokine production by inhibiting the Akt and ERKs pathways, suggesting an anti-inflammatory effect for kefiran.

  1. A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain

    Directory of Open Access Journals (Sweden)

    Sakamoto Atsuhiro

    2011-01-01

    Full Text Available Abstract Background Local anesthetics alleviate neuropathic pain in some cases in clinical practice, and exhibit longer durations of action than those predicted on the basis of the pharmacokinetics of their blocking effects on voltage-dependent sodium channels. Therefore, local anesthetics may contribute to additional mechanisms for reversal of the sensitization of nociceptive pathways that occurs in the neuropathic pain state. In recent years, spinal glial cells, microglia and astrocytes, have been shown to play critical roles in neuropathic pain, but their participation in the analgesic effects of local anesthetics remains largely unknown. Results Repetitive epidural administration of ropivacaine reduced the hyperalgesia induced by chronic constrictive injury of the sciatic nerve. Concomitantly with this analgesia, ropivacaine suppressed the increases in the immunoreactivities of CD11b and glial fibrillary acidic protein in the dorsal spinal cord, as markers of activated microglia and astrocytes, respectively. In addition, epidural administration of a TrkA-IgG fusion protein that blocks the action of nerve growth factor (NGF, which was upregulated by ropivacaine in the dorsal root ganglion, prevented the inhibitory effect of ropivacaine on microglia, but not astrocytes. The blockade of NGF action also abolished the analgesic effect of ropivacaine on neuropathic pain. Conclusions Ropivacaine provides prolonged analgesia possibly by suppressing microglial activation in an NGF-dependent manner and astrocyte activation in an NGF-independent manner in the dorsal spinal cord. Local anesthetics, including ropivacaine, may represent a new approach for glial cell inhibition and, therefore, therapeutic strategies for neuropathic pain.

  2. 76 FR 22610 - Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin

    Science.gov (United States)

    2011-04-22

    .... FDA-2011-N-0003] Implantation or Injectable Dosage Form New Animal Drugs; Enrofloxacin AGENCY: Food... the indications for use of enrofloxacin solution in cattle, as a single injection, for the treatment... supplement to NADA 141-068 for BAYTRIL 100 (enrofloxacin), an injectable solution. The supplemental NADA...

  3. Crocin Suppresses LPS-Stimulated Expression of Inducible Nitric Oxide Synthase by Upregulation of Heme Oxygenase-1 via Calcium/Calmodulin-Dependent Protein Kinase 4

    Directory of Open Access Journals (Sweden)

    Ji-Hee Kim

    2014-01-01

    Full Text Available Crocin is a water-soluble carotenoid pigment that is primarily used in various cuisines as a seasoning and coloring agent, as well as in traditional medicines for the treatment of edema, fever, and hepatic disorder. In this study, we demonstrated that crocin markedly induces the expression of heme oxygenase-1 (HO-1 which leads to an anti-inflammatory response. Crocin inhibited inducible nitric oxide synthase (iNOS expression and nitric oxide production via downregulation of nuclear factor kappa B activity in lipopolysaccharide- (LPS- stimulated RAW 264.7 macrophages. These effects were abrogated by blocking of HO-1 expression or activity. Crocin also induced Ca2+ mobilization from intracellular pools and phosphorylation of Ca2+/calmodulin-dependent protein kinase 4 (CAMK4. CAMK4 knockdown and kinase-dead mutant inhibited crocin-mediated HO-1 expression, Nrf2 activation, and phosphorylation of Akt, indicating that HO-1 expression is mediated by CAMK4 and that Akt is a downstream mediator of CAMK4 in crocin signaling. Moreover, crocin-mediated suppression of iNOS expression was blocked by CAMK4 inhibition. Overall, these results suggest that crocin suppresses LPS-stimulated expression of iNOS by inducing HO-1 expression via Ca2+/calmodulin-CAMK4-PI3K/Akt-Nrf2 signaling cascades. Our findings provide a novel molecular mechanism for the inhibitory effects of crocin against endotoxin-mediated inflammation.

  4. The Effects of Xiangqing Anodyne Spray on Treating Acute Soft-Tissue Injury Mainly Depend on Suppressing Activations of AKT and p38 Pathways

    Directory of Open Access Journals (Sweden)

    Shudong Wang

    2016-01-01

    Full Text Available Objectives. In the present study we try to elucidate the mechanism of Xiangqing anodyne spray (XQAS effects on acute soft-tissue injury (STI. Methods. Acute STI model was established by hammer blow in the rat hind leg muscle. Within 8 hours, instantly after modeling and per 2-hour interval repeated topical applications with or without XQAS, CP or IH ethanol extracts spray (CPS and IHS were performed, respectively; muscle swelling rate and inflammation-related biochemical parameters, muscle histological observation, and mRNA and protein expression were then examined. Results. XQAS dose-dependently suppressed STI-caused muscle swelling, proinflammatory mediator productions, and oxidative stress as well as severe pathological changes in the injured muscle tissue. Moreover, CPS mainly by blocking p38 activation while IHS majorly by blocking AKT activation led to cytoplastic IκBα degradation with NF-κB p65 translocated into the nucleus. There are synergistic effects between CP and IH components in the XQAS on preventing from acute STI with suppressing IκBα degradation, NF-κB p65 translocation, and subsequent inflammation and oxidative stress-related abnormality. Conclusion. Marked effects of XQAS on treating acute STI are ascribed to strong anti-inflammatory and antioxidative actions with a reasonable combination of CP active components, blocking p38-NF-κB pathway activated, and IH active components, blocking AKT-NF-κB pathway activated.

  5. groE mutants of Escherichia coli are defective in umuDC-dependent UV mutagenesis

    International Nuclear Information System (INIS)

    Donnelly, C.E.; Walker, G.C.

    1989-01-01

    Overexpression of the SOS-inducible umuDC operon of Escherichia coli results in the inability of these cells to grow at 30 degrees C. Mutations in several heat shock genes suppress this cold sensitivity. Suppression of umuD+C+-dependent cold sensitivity appears to occur by two different mechanisms. We show that mutations in lon and dnaK heat shock genes suppress cold sensitivity in a lexA-dependent manner. In contrast, mutations in groES, groEL, and rpoH heat shock genes suppress cold sensitivity regardless of the transcriptional regulation of the umuDC genes. We have also found that mutations in groES and groEL genes are defective in umuDC-dependent UV mutagenesis. This defect can be suppressed by increased expression of the umuDC operon. The mechanism by which groE mutations affect umuDC gene product function may be related to the stability of the UmuC protein, since the half-life of this protein is shortened because of mutations at the groE locus

  6. Reducing glucocorticoid dosage improves serum osteocalcin in patients with rheumatoid arthritis-results from the TOMORROW study.

    Science.gov (United States)

    Tada, M; Inui, K; Sugioka, Y; Mamoto, K; Okano, T; Koike, T; Nakamura, H

    2016-02-01

    Decreasing the daily dose of glucocorticoids improved bone metabolic marker levels in patients with rheumatoid arthritis. However, changes in disease activity did not influence bone metabolism. Bone metabolism might thus remain uncontrolled even if disease activity is under good control. Decreasing glucocorticoid dosage appears important for improving bone metabolism. Patients with rheumatoid arthritis (RA) develop osteoporosis more frequently than healthy individuals. Bone resorption is increased and bone formation is inhibited in patients with RA, and glucocorticoid negatively affects bone metabolism. We aimed to investigate factors influencing bone metabolic markers in patients with RA. We started the 10-year prospective cohort Total Management of Risk Factors in Rheumatoid Arthritis Patients to Lower Morbidity and Mortality (TOMORROW) study in 2010. We compared changes in urinary cross-linked N-telopeptide of type I collagen (uNTx) and serum osteocalcin (OC), as markers of bone resorption and formation, respectively, in 202 RA patients and age- and sex-matched volunteers between 2010 and 2011. We also investigated factors influencing ΔuNTx and ΔOC in the RA group using multivariate analysis. Values of ΔuNTx were significantly lower in patients with RA than in healthy controls (-0.51 vs. 7.41 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); p = 0.0013), whereas ΔOC values were significantly higher in RA patients (0.94 vs. 0.37 ng/ml; p = 0.0065). Changes in prednisolone dosage correlated negatively with ΔOC (β = -0.229, p = 0.001), whereas changes in disease activity score, bisphosphonate therapy, and period of biologics therapy did not correlate significantly with ΔOC. No significant correlation was seen between ΔuNTx and change in prednisolone dosage. Decreased glucocorticoid dosage improved bone metabolic markers in RA, but disease activity, bisphosphonate therapy, and period of biologics therapy did not influence

  7. Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings

    Science.gov (United States)

    Trigo, Jose M.; Lagzdins, Dina; Rehm, Jürgen; Selby, Peter; Gamaleddin, Islam; Fischer, Benedikt; Barnes, Allan J.; Huestis, Marilyn A.; Le Foll, Bernard

    2016-01-01

    Background There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ9-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects. Methods Participants underwent an 8-week double-blind placebo-controlled trial (an ABACADAE design), with four smoke as usual conditions (SAU) (A) separated by four cannabis abstinence conditions (B–E), with administration of either self-titrated/fixed doses of placebo or Sativex (up to 108 mg THC/100 mg CBD). The order of medication administration during abstinence conditions was randomized and counterbalanced. Withdrawal symptoms and craving were assessed using the Cannabis Withdrawal Scale (CWS), Marijuana Withdrawal Checklist (MWC) and Marijuana Craving Questionnaire (MCQ). Medication use was assessed during the study by means of self-reports, vial weight control, toxicology and metabolite analysis. Cannabis use was assessed by means of self-reports. Results High fixed doses of Sativex were well tolerated and significantly reduced cannabis withdrawal during abstinence, but not craving, as compared to placebo. Self-titrated doses were lower and showed limited efficacy as compared to high fixed doses. Participants reported a significantly lower “high” following Sativex or placebo as compared to SAU conditions. Cannabis/medication use along the study, as per self-reports, suggests compliance with the study conditions. Conclusions The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence. PMID:26925704

  8. Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings.

    Science.gov (United States)

    Trigo, Jose M; Lagzdins, Dina; Rehm, Jürgen; Selby, Peter; Gamaleddin, Islam; Fischer, Benedikt; Barnes, Allan J; Huestis, Marilyn A; Le Foll, Bernard

    2016-04-01

    There is currently no pharmacological treatment approved for cannabis dependence. In this proof of concept study, we assessed the feasibility/effects of fixed and self-titrated dosages of Sativex (1:1, Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD)) on craving and withdrawal from cannabis among nine community-recruited cannabis-dependent subjects. Participants underwent an 8-week double-blind placebo-controlled trial (an ABACADAE design), with four smoke as usual conditions (SAU) (A) separated by four cannabis abstinence conditions (B-E), with administration of either self-titrated/fixed doses of placebo or Sativex (up to 108 mg THC/100 mg CBD). The order of medication administration during abstinence conditions was randomized and counterbalanced. Withdrawal symptoms and craving were assessed using the Cannabis Withdrawal Scale (CWS), Marijuana Withdrawal Checklist (MWC) and Marijuana Craving Questionnaire (MCQ). Medication use was assessed during the study by means of self-reports, vial weight control, toxicology and metabolite analysis. Cannabis use was assessed by means of self-reports. High fixed doses of Sativex were well tolerated and significantly reduced cannabis withdrawal during abstinence, but not craving, as compared to placebo. Self-titrated doses were lower and showed limited efficacy as compared to high fixed doses. Participants reported a significantly lower "high" following Sativex or placebo as compared to SAU conditions. Cannabis/medication use along the study, as per self-reports, suggests compliance with the study conditions. The results found in this proof of concept study warrant further systematic exploration of Sativex as a treatment option for cannabis withdrawal and dependence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Radiation dosages absorbed by the skin during videofluorographic examination of velopharyngeal function

    International Nuclear Information System (INIS)

    Ohara, Hirotoshi; Ogata, Hisao; Nakajima, Tatsuo; Sone, Kiyoaki

    2008-01-01

    Radiographic assessment has become essential in examining the function of the soft palate and pharyngeal walls in patients with velopharyngeal insufficiency. However, in our search of the literature, there was no report on the exposure dose during videofluorographic examination of velopharyngeal function in Japan. Radiation dosages from videofluorography were measured by attaching a glass dosimeter to the submental skin in 17 patients undergoing examination of velopharyngeal function. Sixteen patients underwent a complete videofluorographic examination. For these 16 patients, the mean time of examination was 96.4 sec; the mean radiation dosage absorbed by the skin was 14.4 mGy, equivalent to approximately 7 standard skull x-rays and lower than that during other fluoroscopic procedures. This dose was also lower than the threshold dose at which the skin damage occurs. In light of increasing concern among the general public over radiation exposure, we consider that these data should provide useful information to patients being asked to give informed consent for this examination. (author)

  10. RP-HPLC Method for the Estimation of Nebivolol in Tablet Dosage Form

    Directory of Open Access Journals (Sweden)

    M. K. Sahoo

    2009-01-01

    Full Text Available A reverse phase HPLC method is described for the determination of nebivolol in tablet dosage form. Chromatography was carried on a Hypersil ODS C18 column using a mixture of methanol and water (80:20 v/v as the mobile phase at a flow rate of 1.0 mL/min with detection at 282 nm. Chlorzoxazone was used as the internal standard. The retention times were 3.175 min and 4.158 min for nebivolol and chlorzoxazone respectively. The detector response was linear in the concentration of 1-400 μg/mL. The limit of detection and limit of quantification was 0.0779 and 0.2361 μg/mL respectively. The percentage assay of nebivolol was 99.974%. The method was validated by determining its sensitivity, accuracy and precision. The proposed method is simple, fast, accurate and precise and hence can be applied for routine quality control of nebivolol in bulk and tablet dosage form.

  11. Fluorometric determination of uranium in urine; Dosage fluorimetrique de l'uranium urinaire

    Energy Technology Data Exchange (ETDEWEB)

    Ronteix, C; Hugot, G [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1960-07-01

    For the medical supervision of personnel the most sensitive analytical methods must be used. The fluorimetric method, enabling determinations to be made without previous concentration, is undoubtedly the quickest and most effective. This report is intended to help users of the method to avoid loss of time in the practical application. It therefore describes in great detail the material used, and also gives precise technical information acquired by experience. (author) [French] Pour la surveillance medicale du personnel, il est necessaire d'utiliser les methodes de dosages les plus sensibles. La methode fluorimetrique qui permet d'effectuer le dosage sans concentration prealable est, sans conteste, la plus rapide et la plus efficace. Le present rapport a pour but de permettre aux utilisateurs de cette methode, d'eviter des pertes de temps dans l'application pratique. Il contient donc, tres detaille, le materiel utilise ainsi que des precisions techniques acquises par l'experience. (auteur)

  12. A model for the calculation of vent clearing transients in pressure suppression systems

    International Nuclear Information System (INIS)

    Brosche, D.

    1975-01-01

    For the layout of a pressure suppression system of a light water cooled reactor (boiling water reactor) it is important to know the time dependent behavior of the vent clearing transient after a loss-of-coolant accident for two main reasons: time of the end of the vent clearing transient influences strongly the pressure and temperature maxima in the drywell and wetwell. Time-dependent behavior of the vent clearing transient influences pressure loads in the condensation pool of the wetwell and therefore pressure induced stresses to the structure. The time-dependent behavior of the water masses in the vent pipes and wetwell are described by the basic equations for a nonstationary incompressible friction flow: momentum equation, continuity equation and a correlation for the variation of the state of the gas volume in the wetwell above the water level. After many algebraic operations and integrations along the flow path, a single ordinary nonlinear differential equation for the variations of the water levels in the vent pipes and wetwell is obtained. Therefore the time-dependent velocities and accelerations of the water levels and the moment of the end clearing transient are known. The time-dependent pressure behavior in the drywell, geometrical conditions, initial submergence depth of the vent pipes and different friction and pressure loss factors are presented. The theoretical model has been tested at corresponding experiments performed at a full scale 1/48 segment of the Humboldt Bay pressure suppression containment in the USA and at the pressure suppression containment at the Marviken nuclear power station in Sweden. All these comparisons have shown good agreement between theory and experiment

  13. Early-life exposure to Tris(1,3-dichloroisopropyl) phosphate induces dose-dependent suppression of sexual behavior in male rats.

    Science.gov (United States)

    Kamishima, Manami; Hattori, Tatsuya; Suzuki, Go; Matsukami, Hidenori; Komine, Chiaki; Horii, Yasuyuki; Watanabe, Gen; Oti, Takumi; Sakamoto, Hirotaka; Soga, Tomoko; Parhar, Ishwar S; Kondo, Yasuhiko; Takigami, Hidetaka; Kawaguchi, Maiko

    2018-05-01

    Exposure to endocrine-disrupting chemicals may adversely affect animals, particularly during development. Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) is an organophosphate with anti-androgen function in vitro that is present in indoor dust at relatively high concentrations. In male rats, androgens are necessary for the development of reproductive organs, as well as the endocrine and central nervous systems. However, we currently do not know the exact effects of TDCIPP exposure through suckling on subsequent reproductive behavior in males. Here, we show that TDCIPP exposure (25-250 mg kg -1 via oral administration over 28 consecutive days post-birth) suppressed male sexual behavior and reduced testes size. These changes were dose-dependent and appeared first in adults rather than in juveniles. These results demonstrate that TDCIPP exposure led to normal body growth and appearance in juveniles, but disrupted the endocrine system and physiology in adults. Therefore, assays should be performed using adult animals to ensure accuracy, and to confirm the influence of chemical substances given during early mammalian life. Copyright © 2017 John Wiley & Sons, Ltd.

  14. The effects of different enrofloxacin dosages on clinical efficacy and resistance development in chickens experimentally infected with Salmonella Typhimurium.

    Science.gov (United States)

    Li, Jun; Hao, Haihong; Cheng, Guyue; Wang, Xu; Ahmed, Saeed; Shabbir, Muhammad Abu Bakr; Liu, Zhenli; Dai, Menghong; Yuan, Zonghui

    2017-09-15

    To investigate the optimal dosage which can improve clinical efficacy and minimize resistance, pharmacokinetics/pharmacodynamics model of enrofloxacin was established. Effect of enrofloxacin treatments on clearance of Salmonella in experimentally infected chickens and simultaneously resistance selection in Salmonella and coliforms were evaluated in three treatment groups (100, PK/PD designed dosage of 4, 0.1 mg/kg b.w.) and a control group. Treatment duration was three rounds of 7-day treatment alternated with 7-day withdrawal. Results showed that 100 mg/kg b.w. of enrofloxacin completely eradicated Salmonella, but resistant coliforms (4.0-60.8%) were selected from the end of the second round's withdrawal period till the end of the experiment (days 28-42). PK/PD based dosage (4 mg/kg b.w.) effectively reduced Salmonella for the first treatment duration. However upon cessation of medication, Salmonella repopulated chickens and persisted till the end with reduced susceptibility (MIC CIP  = 0.03-0.25 mg/L). Low frequency (5-9.5%) of resistant coliforms was selected (days 39-42). Enrofloxacin at dosage of 0.1 mg/kg b.w. was not able to eliminate Salmonella and selected coliforms with slight decreased susceptibility (MIC ENR  = 0.25 mg/L). In conclusion, short time treatment (7 days) of enrofloxacin at high dosage (100 mg/kg b.w.) could be effective in treating Salmonella infection while minimizing resistance selection in both Salmonella and coliforms.

  15. Pressure suppression pool thermal mixing

    International Nuclear Information System (INIS)

    Cook, D.H.

    1984-01-01

    A model is developed and verified to describe the thermal mixing that occurs in the pressure suppression pool (PSP) of a commercial BWR. The model is designed specifically for a Mark-I containment and is intended for use in severe accident sequence analyses. The model produces space and time dependent temperature results throughout the PSP and is useful for evaluating the bulk PSP thermal mixing, the condensation effectiveness of the PSP, and the long-term containment integrity. The model is designed to accommodate single or multiple discharging T-quenchers, a PSP circumferential circulation induced by the residual heat removal system discharge, and the thermal stratification of the pool that occurs immediately after the relief valves close. The PSP thermal mixing model is verified by comparing the model predicted temperatures to experimental temperatures that were measured in an operating BWR suppression pool. The model is then used to investigate several PSP thermal mixing problems that include the time to saturate at full relief valve flow, the temperature response to a typical stuck open relief valve scenario, and the effect of operator rotation of the relief valve discharge point

  16. Screening for suppression in young children: the Polaroid Suppression test

    NARCIS (Netherlands)

    Pott, J.W.R.; Oosterveen, DK; Van Hof-van Duin, J

    1998-01-01

    Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in

  17. Clinical criteria for medical staff exposure and reference dosage within the Galician health Service

    International Nuclear Information System (INIS)

    Garcia Comesana, J.

    2003-01-01

    The generalised use of ionising radiation tests is making these tests become the prime cause of exposure to artificial radiation, receiving one sixth of the dosage through background radiation. (Author)

  18. Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

    Science.gov (United States)

    Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

    2016-08-01

    The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

  19. Plasma levels and symptom complaints in patients maintained on daily dosage of methadone hydrochloride.

    Science.gov (United States)

    Horns, W H; Rado, M; Goldstein, A

    1975-06-01

    Plasma methadone levels, symptom complaints, and urine tests for illicit opiate use were followed weekly in 17 patients on a methadone maintenance program. There were very large differences between patients in the plasma level established at a given dosage, implying large differences in the rate of methadone metabolism. Despite virtually constant daily dosage, the plasma methadone levels fluctuated greatly from week to week and from day to day in individual patients. With rate exceptions there was no relationship between plasma methadone level and symptom complaints or between weekly chamges in plasma methadone level and changes in symptom complaints. Except possible to identify the ocassional patient with unusually low plasam methadone levels, the determination of methadone levels is not likely to be or practical value in methadone programs.

  20. Enalapril dosage in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Elung-Jensen, Thomas; Heisterberg, Jens; Sonne, Jesper

    2005-01-01

    OBJECTIVE: In chronic renal failure, clearance of enalapril is reduced. Hence, a renoprotective effect may be achieved with lower doses than conventionally used. Since marked inter-patient variation in concentrations of enalaprilat has been shown in patients with renal failure despite equivalent...... dosage of enalapril, a direct comparison of the effect of high versus low plasma concentrations of enalaprilat on the progression of renal failure was undertaken. METHODS: Forty patients with a median glomerular filtration rate (GFR) of 17 (6-35) ml/min/1.73 m2 were studied in an open-label, randomised...... intervals by the plasma clearance of 51Cr-EDTA, and the individual rates of progression of renal failure were calculated as the slope of GFR versus time plot. RESULTS: In the high-concentration group, the median enalaprilat trough concentration was 92.9 ng/ml (21.8-371.0 ng/ml) and in the low...

  1. A novel solid dosage form of rifampicin and isoniazid with improved functionality.

    Science.gov (United States)

    Gohel, Mukesh C; Sarvaiya, Krishnakant G

    2007-08-24

    The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%-4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.

  2. Suppressing an anti-inflammatory cytokine reveals a strong age-dependent survival cost in mice.

    Directory of Open Access Journals (Sweden)

    Virginia Belloni

    Full Text Available BACKGROUND: The central paradigm of ecological immunology postulates that selection acts on immunity as to minimize its cost/benefit ratio. Costs of immunity may arise because the energetic requirements of the immune response divert resources that are no longer available for other vital functions. In addition to these resource-based costs, mis-directed or over-reacting immune responses can be particularly harmful for the host. In spite of the potential importance of immunopathology, most studies dealing with the evolution of the immune response have neglected such non resource-based costs. To keep the immune response under control, hosts have evolved regulatory pathways that should be considered when studying the target of the selection pressures acting on immunity. Indeed, variation in regulation may strongly modulate the negative outcome of immune activation, with potentially important fitness consequences. METHODOLOGY/PRINCIPAL FINDINGS: Here, we experimentally assessed the survival costs of reduced immune regulation by inhibiting an anti-inflammatory cytokine (IL-10 with anti-IL-10 receptor antibodies (anti-IL-10R in mice that were either exposed to a mild inflammation or kept as control. The experiment was performed on young (3 months and old (15 months individuals, as to further assess the age-dependent cost of suppressing immune regulation. IL-10 inhibition induced high mortality in old mice exposed to the mild inflammatory insult, whereas no mortality was observed in young mice. However, young mice experienced a transitory lost in body mass when injected with the anti-IL-10R antibodies, showing that the treatment was to a lesser extent also costly for young individuals. CONCLUSIONS: These results suggest a major role of immune regulation that deserves attention when investigating the evolution of immunity, and indicate that the capacity to down-regulate the inflammatory response is crucial for late survival and longevity.

  3. Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

    Science.gov (United States)

    Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

    2012-06-01

    What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

  4. Mechanisms of cross-suppression of TNP-specific plaque forming cell responses by TMA-specific first-order T suppressor factor

    Energy Technology Data Exchange (ETDEWEB)

    Jendrisak, G.S.; Bellone, C.J.

    1986-03-05

    The addition of hybridoma-derived phenyltrimethylammonium (TMA)-specific first-order T suppressor factor (TsF/sub 1/) into cultures containing Brucella abortus coupled with the TMA and trinitrophenol haptens (TMA-BA-TNP) results in the cross-suppression of TNP-specific plaque forming cell (PFC) responses. The suppression mediated by TMA-TsF/sub 1/ is dependent on the presence of T cells and specific antigen (TMA). Subculturing of whole spleen cells with TMA-TsF/sub 1/ and specific soluble antigen (TMA-BSA) is able to induce suppressor T cells which cross-suppress the TNP-specific PFC of spleen cell cultures stimulated with TMA-BA-TNP in an antigen (TMA)-dependent manner at the effector phase of the response. The effector acting T suppressor cells (Tse) are nylon wool nonadherent and appears to require whole spleen cells in responding cultures for suppression, suggesting that the target of the Tse is not the TNP-specific B cell. The authors are presently characterizing the mechanisms of cross-suppression by TMA-TsF/sub 1/ and Tse utilizing the described primary in vitro antibody assay.

  5. Feeding blueberry diets to young rats dose-dependently inhibits bone resorption through suppression of RANKL in stromal cells.

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    Full Text Available Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB powder for two weeks beginning on postnatal day 21 (PND21 significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is, as yet, unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5% for 35 days beginning on PND25 on bone quality, and osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT of tibia, demonstrated that bone mineral density (BMD and content (BMC were dose-dependently increased in BB-fed rats compared to controls (P<0.05. Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-κB ligand a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPARγ (peroxisome proliferator-activated receptor γ which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption.

  6. Maintenance and Loss of Duplicated Genes by Dosage Subfunctionalization.

    Science.gov (United States)

    Gout, Jean-Francois; Lynch, Michael

    2015-08-01

    Whole-genome duplications (WGDs) have contributed to gene-repertoire enrichment in many eukaryotic lineages. However, most duplicated genes are eventually lost and it is still unclear why some duplicated genes are evolutionary successful whereas others quickly turn to pseudogenes. Here, we show that dosage constraints are major factors opposing post-WGD gene loss in several Paramecium species that share a common ancestral WGD. We propose a model where a majority of WGD-derived duplicates preserve their ancestral function and are retained to produce enough of the proteins performing this same ancestral function. Under this model, the expression level of individual duplicated genes can evolve neutrally as long as they maintain a roughly constant summed expression, and this allows random genetic drift toward uneven contributions of the two copies to total expression. Our analysis suggests that once a high level of imbalance is reached, which can require substantial lengths of time, the copy with the lowest expression level contributes a small enough fraction of the total expression that selection no longer opposes its loss. Extension of our analysis to yeast species sharing a common ancestral WGD yields similar results, suggesting that duplicated-gene retention for dosage constraints followed by divergence in expression level and eventual deterministic gene loss might be a universal feature of post-WGD evolution. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Radiation exposure to nuclear medicine technologists from administering I-131 therapy dosages

    International Nuclear Information System (INIS)

    Chaudakshetrin, P.; Pusuwan, P.; Sritongkul, N.; Tuntawiroon, M.

    2007-01-01

    Full text: Therapeutic doses of I-131 for treatment of thyroid cancer are administered orally in liquid or capsule form. During the last few years, a total number of patients loaded in our isolation ward increased from 4 to 10 patients per week. When considering radiation safety precautions for attending technologists, it is preferable to use the dose in capsules. The purpose of this study is to compare radiation exposure to nuclear medicine technologists from administering I-131 therapy dosages in capsules and in liquid form in a closed system. Materials and Methods: Three year radiation exposure to technologists during I-131 administration was analyzed. From January 2004 to June 2005 dose administration was in liquid form (n=263) and from July 2005 to February 2007 in capsules (n=541). Radiation dose assessment was performed with an electronic personal dosimeter (PDM 112). The dose rate in μSv and time spent per patient were recorded. Results: Dose received per patient when I-131 was given in a liquid was 3.50 ± 1.67 μSv and 1.17 ± 0.66 μSv when given in capsules. Compared with the use of a liquid, capsules significantly reduced radiation dose to technologists by 66% (P < 0.001). These doses received depended not only on the administered activity but also on the time, distance and shielding. Time spent per patient, including a brief visit before the time of dosing to explain the procedure and answer questions was reduced slightly from 4.4 ± 2.2 to 3.7 ± 1.8 minutes (P < 0.01). These correspond to a reduction in a yearly dose to 1 technologist by 40%, from 0.63 mSv to 0.38 mSv from dosing to 175 and 325 patients respectively. Conclusions: The measured doses clearly showed that handling of I-131 therapy dosages either in a liquid form or capsules are not the major contributors to the technologist's radiation exposure in routine clinical practice. However, one has to be cautious and follow good work practice to avoid risk of radiation exposure and radioiodine

  8. Tagging and suppression of pileup jets

    CERN Document Server

    The ATLAS collaboration

    2014-01-01

    The suppression of pileup jets has been a crucial component of many physics analyses using 2012 LHC proton-proton collisions. In ATLAS, tracking information has been used to calculate a variable called the jet-vertex-fraction, which is the fraction of the total mo- mentum of tracks in the jet which is associated to the primary vertex. Imposing a minimum on this variable rejects the majority of pileup jets, but leads to hard-scatter jet efficiencies that depend on the number of reconstructed primary vertices in the event ($N_{Vtx}$). In this note, new track-based variables to suppress pileup jets are developed in such a way that the resulting hard-scatter jet efficiency is stable as a function of $N_{Vtx}$. A multivariate combina- tion of two such variables called the jet-vertex-tagger is constructed. In addition, it is shown that jet-vertex association can be applied to large-R jets, providing a track-based grooming technique that is as powerful as calorimeter-based trimming but based on complementary trackin...

  9. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

    Science.gov (United States)

    Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

    2015-09-01

    Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.

  10. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp

    2015-05-15

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.

  11. DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

    International Nuclear Information System (INIS)

    Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya

    2015-01-01

    Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action

  12. Maximum a posteriori Bayesian estimation of mycophenolic Acid area under the concentration-time curve: is this clinically useful for dosage prediction yet?

    Science.gov (United States)

    Staatz, Christine E; Tett, Susan E

    2011-12-01

    This review seeks to summarize the available data about Bayesian estimation of area under the plasma concentration-time curve (AUC) and dosage prediction for mycophenolic acid (MPA) and evaluate whether sufficient evidence is available for routine use of Bayesian dosage prediction in clinical practice. A literature search identified 14 studies that assessed the predictive performance of maximum a posteriori Bayesian estimation of MPA AUC and one report that retrospectively evaluated how closely dosage recommendations based on Bayesian forecasting achieved targeted MPA exposure. Studies to date have mostly been undertaken in renal transplant recipients, with limited investigation in patients treated with MPA for autoimmune disease or haematopoietic stem cell transplantation. All of these studies have involved use of the mycophenolate mofetil (MMF) formulation of MPA, rather than the enteric-coated mycophenolate sodium (EC-MPS) formulation. Bias associated with estimation of MPA AUC using Bayesian forecasting was generally less than 10%. However some difficulties with imprecision was evident, with values ranging from 4% to 34% (based on estimation involving two or more concentration measurements). Evaluation of whether MPA dosing decisions based on Bayesian forecasting (by the free website service https://pharmaco.chu-limoges.fr) achieved target drug exposure has only been undertaken once. When MMF dosage recommendations were applied by clinicians, a higher proportion (72-80%) of subsequent estimated MPA AUC values were within the 30-60 mg · h/L target range, compared with when dosage recommendations were not followed (only 39-57% within target range). Such findings provide evidence that Bayesian dosage prediction is clinically useful for achieving target MPA AUC. This study, however, was retrospective and focussed only on adult renal transplant recipients. Furthermore, in this study, Bayesian-generated AUC estimations and dosage predictions were not compared

  13. Rheology as a tool for evaluation of melt processability of innovative dosage forms

    DEFF Research Database (Denmark)

    Aho, Johanna Maaria; Boetker, Johan P; Baldursdottir, Stefania

    2015-01-01

    ) printing, will have an increasingly important role when designing products for flexible dosing, since dosage forms based on compacting of a given powder mixture do not enable manufacturing of optimal pharmaceutical products for personalized treatments. The melt processability of polymers and API...

  14. A Novel Disintegration Tester for Solid Dosage Forms Enabling Adjustable Hydrodynamics.

    Science.gov (United States)

    Kindgen, Sarah; Rach, Regine; Nawroth, Thomas; Abrahamsson, Bertil; Langguth, Peter

    2016-08-01

    A modified in vitro disintegration test device was designed that enables the investigation of the influence of hydrodynamic conditions on disintegration of solid oral dosage forms. The device represents an improved derivative of the compendial PhEur/USP disintegration test device. By the application of a computerized numerical control, a variety of physiologically relevant moving velocities and profiles can be applied. With the help of computational fluid dynamics, the hydrodynamic and mechanical forces present in the probe chamber were characterized for a variety of device moving speeds. Furthermore, a proof of concept study aimed at the investigation of the influence of hydrodynamic conditions on disintegration times of immediate release tablets. The experiments demonstrated the relevance of hydrodynamics for tablet disintegration, especially in media simulating the fasted state. Disintegration times increased with decreasing moving velocity. A correlation between experimentally determined disintegration times and computational fluid dynamics predicted shear stress on tablet surface was established. In conclusion, the modified disintegration test device is a valuable tool for biorelevant in vitro disintegration testing of solid oral dosage forms. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  15. Effect of 18F-FDG dosage alternation on final PET image

    International Nuclear Information System (INIS)

    Yin Dayi; Yao Shulin; Chen Yingmao; Shao Mingzhe; Tian Jiahe

    2002-01-01

    Objective: To assess PET reconstructed image effected by different 18 F-FDG dosages with quantitative and qualitative analysis. Methods: To perform PET phantom acquisition by routine clinical parameters after filled with different doses of 18 F-FDG solution. An identical slice was extracted from reconstructed image for doing following analysis: the hot area standard uptake value (SUV), the ratio of hot area to cold area, the standard deviation on background area, the ratio of true coincidence to random. Results: 296 MBq: The image uniformity was terribly worse, T/R=0.83, other indexes were irregular. 148 MBq: The image presentation looked like the image without attenuation correction, T/R=1.64, other indexes were moderate. 74, 37 and 18.5 MBq: The images were with excellent uniformity, resolution and contrast, the background noise was suitable, all of the quantitative indexes were good. 9.25 and 4.625 MBq: The uniformity and resolution was degraded terribly because of the higher noise and lower information. Conclusion: Combining above results with other considerations, such as radiation exposure, information amount and acquisition time, the authors think the optimal dosage should be 4.625-11.1 MBq/kg

  16. Preparation and characterization of solid oral dosage forms containing soy isoflavones

    Directory of Open Access Journals (Sweden)

    Stela R. de Oliveira

    2013-02-01

    Full Text Available Soy isoflavones have been extensively used for menopausal symptoms and prevention of hormone-related cancer, osteoporosis and cardiovascular diseases. Commercially available forms of isoflavones include supplements, capsules and tablets. However, the non-standardization of soy isoflavones extracts and different dissolution profiles of these solid dosage forms highlight the need of additional studies on the development of well characterized pharmaceutical dosage forms of isoflavones. In this work, immediate release oral tablets of soy isoflavones were obtained and evaluated. Genistein and daidzein, were the main constituents of the dried soy extract. Preparation of the tables was accomplished in a rotary tableting machine following either a dry mixture for direct compression or wet granulation with different excipients. Powder, granules and tablets were evaluated for several parameters, including flow properties, Carr and Hausner indexes, hardness, friability, disintegration time and drug release profile. Also, a fast and validated HPLC analytical method for both genistein and daidzein was developed. Formulations containing sodium croscarmellose and sodium dodecyl sulfate resulted in better flowability as indicated by the flow rate and angle of repose, faster disintegration time and immediate release dissolution profile.

  17. Effective Dosage of Midazolam to Erase the Memory of Vascular Pain During Propofol Administration.

    Science.gov (United States)

    Boku, Aiji; Inoue, Mika; Hanamoto, Hiroshi; Oyamaguchi, Aiko; Kudo, Chiho; Sugimura, Mitsutaka; Niwa, Hitoshi

    Intravenous sedation with propofol is often administered to anxious patients in dental practice. Pain on injection of propofol is a common adverse effect. This study aimed to determine the age-adjusted doses of midazolam required to erase memory of vascular pain of propofol administration and assess whether the Ramsay Sedation Scale (RSS) after the pretreatment of midazolam was useful to predict amnesia of the vascular pain of propofol administration. A total of 246 patients with dental phobia requiring dental treatment under intravenous sedation were included. Patients were classified according to their age: 30s, 40s, 50s, and 60s. Three minutes after administration of a predetermined dose of midazolam, propofol was infused continuously. After completion of the dental procedure, patients were interviewed about the memory of any pain or discomfort in the injection site or forearm. The dosage of midazolam was determined using the Dixon up-down method. The first patient was administered 0.03 mg/kg, and if memory of vascular pain remained, the dosage was increased by 0.01 mg/kg for the next patient, and then if the memory was erased, the dosage was decreased by 0.01 mg/kg. The effective dosage of midazolam in 95% of each age group for erasing the memory of propofol vascular pain (ED95) was determined using logistic analysis. The accuracy of RSS to predict the amnesia of injection pain was assessed by receiver operating characteristic (ROC) analysis. The ED95 of midazolam to erase the memory of propofol vascular pain was 0.061 mg/kg in patients in their 30s, 0.049 mg/kg in patients in their 40s, 0.033 mg/kg in patients in their 50s, and 0.033 mg/kg in patients in their 60s. The area under the ROC curve was 0.31. The ED95 of midazolam required to erase the memory of propofol vascular pain demonstrated a downward trend with age. On the other hand, it was impossible to predict the amnesia of propofol vascular pain using the RSS.

  18. Gambogic acid inhibits multiple myeloma mediated osteoclastogenesis through suppression of chemokine receptor CXCR4 signaling pathways.

    Science.gov (United States)

    Pandey, Manoj K; Kale, Vijay P; Song, Chunhua; Sung, Shen-shu; Sharma, Arun K; Talamo, Giampaolo; Dovat, Sinisa; Amin, Shantu G

    2014-10-01

    Bone disease, characterized by the presence of lytic lesions and osteoporosis is the hallmark of multiple myeloma (MM). Stromal cell-derived factor 1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4), has been implicated as a regulator of bone resorption, suggesting that agents that can suppress SDF1α/CXCR4 signaling might inhibit osteoclastogenesis, a process closely linked to bone resorption. We, therefore, investigated whether gambogic acid (GA), a xanthone, could inhibit CXCR4 signaling and suppress osteoclastogenesis induced by MM cells. Through docking studies we predicted that GA directly interacts with CXCR4. This xanthone down-regulates the expression of CXCR4 on MM cells in a dose- and time-dependent manner. The down-regulation of CXCR4 was not due to proteolytic degradation, but rather GA suppresses CXCR4 mRNA expression by inhibiting nuclear factor-kappa B (NF-κB) DNA binding. This was further confirmed by quantitative chromatin immunoprecipitation assay, as GA inhibits p65 binding at the CXCR4 promoter. GA suppressed SDF-1α-induced chemotaxis of MM cells and downstream signaling of CXCR4 by inhibiting phosphorylation of Akt, p38, and Erk1/2 in MM cells. GA abrogated the RANKL-induced differentiation of macrophages to osteoclasts in a dose- and time-dependent manner. In addition, we found that MM cells induced differentiation of macrophages to osteoclasts, and that GA suppressed this process. Importantly, suppression of osteoclastogenesis by GA was mediated through IL-6 inhibition. Overall, our results show that GA is a novel inhibitor of CXCR4 expression and has a strong potential to suppress osteoclastogenesis mediated by MM cells. Published by Elsevier Inc.

  19. Fenofibrate suppresses cellular metabolic memory of high glucose in diabetic retinopathy via a sirtuin 1-dependent signalling pathway.

    Science.gov (United States)

    Zhao, Shuzhi; Li, Jun; Wang, Na; Zheng, Bingqing; Li, Tao; Gu, Qing; Xu, Xun; Zheng, Zhi

    2015-10-01

    Inflammation is a major contributing factor in the development of diabetic microvascular complications, regardless of whether improved glycaemic control is achieved. Studies have increasingly indicated that fenofibrate, a lipid‑lowering therapeutic agent in clinical use, exerts a potential anti‑inflammatory effect, which is mediated by sirtuin 1 (SIRT1; an NAD+‑dependent deacetylase) in endothelial cells. The aim of the present study was to investigate the inhibitory effect of fenofibrate on metabolic memory (via the regulation of SIRT1), and inflammatory responses in cell and animal models of diabetic retinopathy (DR). The data demonstrated that high glucose treatment in human retinal endothelial cells (HRECs) inhibited the expression and deacetylase activity of SIRT1. The reduction of SIRT1 expression and deacetylase activity persisted following a return to normal glucose levels. Furthermore, nuclear factor‑κB expression was observed to be negatively correlated with SIRT1 expression and activity in HRECs under high glucose levels and the subsequent return to normal glucose levels. Fenofibrate treatment abrogated these changes. Knockdown of SIRT1 attenuated the effect of fenofibrate on high glucose‑induced NF‑κB expression. In addition, fenofibrate upregulated SIRT1 expression through peroxisome proliferator‑activated receptor α in high glucose‑induced metabolic memory. These findings indicate that fenofibrate is important in anti‑inflammatory processes and suppresses the cellular metabolic memory of high glucose‑induced stress via the SIRT1‑dependent signalling pathway. Thus, treatment with fenofibrate may offer a promising therapeutic strategy for halting the development of DR and other complications of diabetes.

  20. Apparatus comprising trace element dosage and method for treating raw water in biofilter

    DEFF Research Database (Denmark)

    2015-01-01

    the inlet (2) to the outlet (3) or in the reverse direction, - the trace element dosage device (13) is positioned upstream of the porous filter material and microbial biomass and is configured to dose trace element(s) to the water flowing through the filter. A method for treating raw water by microbial......Apparatus for treating raw water in a biofilter The present invention relates to an apparatus in which raw water is treated through microbial activity where microbial activity is controlled by nutrients and other parameters. Some of the nutrients controlling the microbial activity are trace...... elements such as certain metals (Cu, Co, Cr, Mo, Ni, W, Zn or a mixture thereof). The apparatus comprising - a volume provided with an inlet (2) for raw water and an outlet (3) for water having been subjected to microbial activity, a filter and a trace element dosage device (13) are placed in this volume...

  1. Malavefes: A computational voice-enabled malaria fuzzy informatics software for correct dosage prescription of anti-malarial drugs

    Directory of Open Access Journals (Sweden)

    Olugbenga O. Oluwagbemi

    2018-04-01

    Full Text Available Malaria is one of the infectious diseases consistently inherent in many Sub-Sahara African countries. Among the issues of concern are the consequences of wrong diagnosis and dosage administration of anti-malarial drugs on sick patients; these have resulted into various degrees of complications ranging from severe headaches, stomach and body discomfort, blurred vision, dizziness, hallucinations, and in extreme cases, death. Many expert systems have been developed to support different infectious disease diagnoses, but not sure of any yet, that have been specifically designed as a voice-based application to diagnose and translate malaria patients’ symptomatic data for pre-laboratory screening and correct prescription of proper dosage of the appropriate medication. We developed Malavefes, (a malaria voice-enabled computational fuzzy expert system for correct dosage prescription of anti-malarial drugs using Visual Basic.NET., and Java programming languages. Data collation for this research was conducted by survey from existing literature and interview from public health experts. The database for this malaria drug informatics system was implemented using Microsoft Access. The Root Sum Square (RSS was implemented as the inference engine of Malavefes to make inferences from rules, while Centre of Gravity (CoG was implemented as the defuzzification engine. The drug recommendation module was voice-enabled. Additional anti-malaria drug expiration validation software was developed using Java programming language. We conducted a user-evaluation of the performance and user-experience of the Malavefes software. Keywords: Informatics, Bioinformatics, Fuzzy, Anti-malaria, Voice computing, Dosage prescription

  2. Cancer therapy leading to state of cancer metabolism depression for efficient operation of small dosage cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Ponizovskiy MR

    2015-04-01

    Full Text Available “Prolonged medical starvation” as the method of cancer therapy was borrowed from folk healers Omelchenko A and Breuss R. Author was convinced in efficiency of this method of cancer treatment via examination of cured patients and on own experience. The mechanism of this method of cancer therapy operates via Warburg effect targeting that promotes efficient cancer treatment with small cytotoxic drugs. Just it was described the mechanism of Warburg effect as well as mechanism transmutation of mitochondrial function in cancer metabolism which are exhibited in connection with operation of described method cancer therapy. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission which occur sometimes as result of treatment with great dosage of cytotoxic drugs. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The significance of this work that it was substantiated the mechanism operation of combination “Prolonged medical starvation” with small dosages cytotoxic drugs of cancer treatment, which mechanism leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs in cancer therapy. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments.

  3. Vitamin D supplementation in inflammatory bowel disease: the role of dosage and patient compliance.

    Science.gov (United States)

    Kojecky, V; Adamikova, A; Klimek, P

    2016-01-01

    Vitamin D substitution is recommended in patients with inflammatory bowel disease. Specific guidelines are lacking. The aim of this study was to assess the effect of vitamin D supplementation with respect to dosage and patient compliance. A prospective cohort study of 167 Crohn disease/ulcerative colitis outpatients. Patients were screened for serum vitamin D (25OHD2+3) at the end of summer and in late winter. Demographic data, history of vitamin D supplementation were recorded and matched with prescription records. A total of 57 subjects used vitamin D supplementation (mean dose 1104 IU/day). 25OHD2+3 levels were lower (p compliance with vitamin D supplementation was low, however this fact did not significantly contribute to the degree of vitamin D deficiency in this dosage (Tab. 3, Fig. 1, Ref. 21).

  4. A Validated RP-HPLC Method for the Determination of Atazanavir in Pharmaceutical Dosage Form

    Directory of Open Access Journals (Sweden)

    K. Srinivasu

    2011-01-01

    Full Text Available A validated RP HPLC method for the estimation of atazanavir in capsule dosage form on YMC ODS 150 × 4.6 mm, 5 μ column using mobile phase composition of ammonium dihydrogen phosphate buffer (pH 2.5 with acetonitrile (55:45 v/v. Flow rate was maintained at 1.5 mL/min with 288 nm UV detection. The retention time obtained for atazanavir was at 4.7 min. The detector response was linear in the concentration range of 30 - 600 μg/mL. This method has been validated and shown to be specific, sensitive, precise, linear, accurate, rugged, robust and fast. Hence, this method can be applied for routine quality control of atazanavir in capsule dosage forms as well as in bulk drug.

  5. Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia

    Science.gov (United States)

    Petrovski, Steve; Chan, Hiu Tat; Angove, Michael J.; Tucci, Joseph

    2018-01-01

    The delivery of phages to epithelial surfaces for therapeutic outcomes is a realistic proposal, and indeed one which is being currently tested in clinical trials. This paper reviews some of the known research on formulation of phages into semi-solid dosage forms such as creams, ointments and pastes, as well as solid dosage forms such as troches (or lozenges and pastilles) and suppositories/pessaries, for delivery to the epithelia. The efficacy and stability of these phage formulations is discussed, with a focus on selection of optimal semi-solid bases for phage delivery. Issues such as the need for standardisation of techniques for formulation as well as for assessment of efficacy are highlighted. These are important when trying to compare results from a range of experiments and across different delivery bases. PMID:29495355

  6. Particle Engineering Via Mechanical Dry Coating in the Design of Pharmaceutical Solid Dosage Forms.

    Science.gov (United States)

    Qu, Li; Morton, David A V; Zhou, Qi Tony

    2015-01-01

    Cohesive powders are problematic in the manufacturing of pharmaceutical solid dosage forms because they exhibit poor flowability, fluidization and aerosolization. These undesirable bulk properties of cohesive powders represent a fundamental challenge in the design of efficient pharmaceutical manufacturing processes. Recently, mechanical dry coating has attracted increasing attention as it can improve the bulk properties of cohesive powders in a cheaper, simpler, safer and more environment-friendly way than the existing solvent-based counterparts. In this review, mechanical dry coating techniques are outlined and their potential applications in formulation and manufacturing of pharmaceutical solid dosage forms are discussed. Reported data from the literature have shown that mechanical dry coating holds promise for the design of superior pharmaceutical solid formulations or manufacturing processes by engineering the interfaces of cohesive powders in an efficient and economical way.

  7. Respective roles and interactions of T-lymphocyte and PGE2-mediated monocyte suppressive activities in human newborns and mothers at the time of delivery

    International Nuclear Information System (INIS)

    Durandy, A.; Fischer, A.; Mamas, S.; Dray, F.; Griscelli, C.

    1982-01-01

    Recently the concept of a poorly functional humoral immune response in the newborn was proposed. Data have been presented indicating that the impaired newborn B cell maturation, as shown in vitro in a pokeweed mitogen-induced B cell maturation system, is due both to an immaturity of lymphocyte subsets and to an increased suppressive T activity. In the present work, we present evidence that there exists a predominance of a naturally occurring T lymphocyte suppressive activity in the cord blood in that the removal of the suppressive activity by irradiation allows a normal maturation of newborn B cells. Such normal maturation of newborn B cells can also be obtained using mixed cultures of adult T cells and newborn B cells. Newborn suppressor T cells belong to both EA gamma (+) and EA gamma (-) fractions, and it is not known whether these two groups do or do not belong to different subsets. The PGE2-dependent monocyte suppressive activity does not play any role in the suppression observed in newborns since newborn monocytes are poorly suppressive and since they produce a smaller amount of PGE2 than adult monocytes. Some observations suggest, on the contrary, that the suppressive T lymphocytes can regulate the level of the PGE2-dependent monocyte suppressive activity. It should be noticed that similar observations about T lymphocyte and PGE2-dependent monocyte suppressive activities have been made at the same time using mothers' cells. These observations suggest the possibility that such changes in B cell immune regulation may result from an interaction between maternal and fetal lymphoid cells

  8. Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats.

    Science.gov (United States)

    Gilad, Gad M; Gilad, Varda H

    2013-12-01

    Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21 days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3 g/l agmatine sulfate in their drinking water for 95 days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals' body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20 days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20 days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. parkin mutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism

    Directory of Open Access Journals (Sweden)

    Schellenberg Gerard D

    2005-02-01

    Full Text Available Abstract Background parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage. Methods We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and ≥ 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons. Results Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations. Conclusion Anticipation is not linked to parkin, and may signify a distinct disease entity.

  10. Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway.

    Science.gov (United States)

    Song, Zhi; Zhao, Xiu; Liu, Martin; Jin, Hongxu; Wang, Ling; Hou, Mingxiao; Gao, Yan

    2015-12-01

    Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-κB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-κB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-κB and the degradation of its inhibitor IκB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-κB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  11. Use of fluorescence spectroscopy to control ozone dosage in recirculating aquaculture systems

    DEFF Research Database (Denmark)

    Spiliotopoulou, Aikaterini; Martin, Richard; Pedersen, Lars-Flemming

    2017-01-01

    , in order to optimise ozonation treatment. Water samples from six different Danish facilities (two rearing units from a commercial trout RAS, a commercial eel RAS, a pilot RAS and two marine water aquariums) were treated with different O3 dosages (1.0–20.0 mg/L ozone) in bench-scale experiments, following...

  12. Testosterone Suppression of CRH-stimulated Cortisol in Men

    OpenAIRE

    Rubinow, David R.; Roca, Catherine A.; Schmidt, Peter J.; Danaceau, Merry A.; Putnam, Karen; Cizza, Giovanni; Chrousos, George; Nieman, Lynnette

    2005-01-01

    Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in ten men (ages 18–45) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower ...

  13. Can a static nonlinearity account for the dynamics of otoacoustic emission suppression?

    DEFF Research Database (Denmark)

    Verhulst, Sarah; Shera, Christopher A.; Harte, James

    2011-01-01

    This study investigates whether time-dependent compression mechanisms in the cochlea are necessary to explain dynamic properties of otoacoustic emissions (OAEs). Dynamic properties of click-evoked OAEs (CEOAEs) have been observed in temporal suppression; the effect where the CEOAE magnitude is re...

  14. DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans.

    Science.gov (United States)

    Miyata, Sachiko; Begun, Jakob; Troemel, Emily R; Ausubel, Frederick M

    2008-02-01

    To further understand how the nematode Caenorhabditis elegans defends itself against pathogen attack, we analyzed enhanced pathogen resistance (epr) mutants obtained from a forward genetic screen. We also examined several well-characterized sterile mutants that exhibit an Epr phenotype. We found that sterility and pathogen resistance are highly correlated and that resistance in both epr and sterile mutants is dependent on DAF-16 activity. Our data indicate that a DAF-16-dependent signaling pathway distinct from previously described pathways is involved in the activation of genes that confer resistance to bacterial pathogens. The timing of DAF-16-dependent gene activation in sterile mutants coincides with the onset of embryonic development in wild-type animals, suggesting that signals from developing embryos normally downregulate the immune response.

  15. Aging and repeated thought suppression success.

    Directory of Open Access Journals (Sweden)

    Ann E Lambert

    Full Text Available Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

  16. 76 FR 81806 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    Science.gov (United States)

    2011-12-29

    .... FDA-2011-N-0003] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... solution of ivermectin. DATES: This rule is effective December 29, 2011. FOR FURTHER INFORMATION CONTACT... ANADA 200-318 for [[Page 81807

  17. The impact of intermediate-term alcohol abstinence on memory retrieval and suppression

    Directory of Open Access Journals (Sweden)

    Viola Luca Nemeth

    2014-12-01

    Full Text Available Background: The nature of episodic memory deficit in intermediate-term abstinence from alcohol in alcohol dependence (AD is not yet clarified. Deficits in inhibitory control are commonly reported in substance use disorders. However, much less is known about cognitive control suppressing interference from memory. The Think/No-think (TNT paradigm is a well established method to investigate inhibition of associative memory retrieval.Methods: Thirty-six unmedicated alcohol dependent (AD patients and 36 healthy controls (HC performed the TNT task. Thirty image-word pairs were trained up to a predefined accuracy level. Cued recall was examined in three conditions: Think (T for items instructed to-be-remembered, No-think (NT assessing the ability to suppress retrieval and Baseline (B for general relational memory. Premorbid IQ, clinical variables and impulsivity measures were quantified. Results: AD patients had a significantly increased demand for training. Baseline memory abilities and effect of practice on retrieval were not markedly different between the groups. We found a significant main effect of group (HC vs AD x condition (B, T and NT and a significant difference in mean NT-B scores for the two groups. Discussion: AD and HC groups did not differ essentially in their baseline memory abilities. Also, the instruction to focus on retrieval improved episodic memory performance in both groups. Crucially, control participants were able to suppress relational words in the NT condition supporting the critical effect of cognitive control processes over inhibition of retrieval. In contrast to this, the ability of AD patients to suppress retrieval was found to be impaired.

  18. Dry coating of solid dosage forms: an overview of processes and applications.

    Science.gov (United States)

    Foppoli, Anastasia Anna; Maroni, Alessandra; Cerea, Matteo; Zema, Lucia; Gazzaniga, Andrea

    2017-12-01

    Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both organic solvents and aqueous coating systems can be overcome, such as toxicological, environmental, and safety-related issues on the one hand as well as costly drying phases and impaired product stability on the other. The considerable advantages related to solventless coating has been prompting a strong research interest in this field of pharmaceutics. In the article, processes and applications relevant to techniques intended for dry coating are analyzed and reviewed. Based on the physical state of the coat-forming agents, liquid- and solid-based techniques are distinguished. The former include hot-melt coating and coating by photocuring, while the latter encompass press coating and powder coating. Moreover, solventless techniques, such as injection molding and three-dimensional printing by fused deposition modeling, which are not purposely conceived for coating, are also discussed in that they would open new perspectives in the manufacturing of coated-like dosage forms.

  19. Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review.

    Science.gov (United States)

    Blackshields, Caroline A; Crean, Abina M

    2018-07-01

    There has been a noticeable shift from pharmaceutical batch processing towards a more continuous mode of manufacture for solid oral dosage forms. Continuous solid oral dose processes would not be possible in the absence of a highly accurate feeding system. The performance of feeders defines the content of formulations and is therefore a critical operation in continuous manufacturing of solid dosage forms. It was the purpose of this review to review the role of the initial powder feeding step in a continuous manufacturing process. Different feeding mechanisms are discussed with a particular emphasis on screw controlled loss in weight (LIW) feeding. The importance of understanding the physical properties of the raw materials and its impact on the feeding process is reviewed. Prior knowledge of materials provides an initial indication of how the powders will behave through processing and facilitates in the selection of the most suitable (i) feeder (capacity), (ii) feeding mechanism, and (iii) in the case of screw feeder - screw type. The studies identified in this review focus on the impact of material on powder feeding performance.

  20. Warfarin dosage response related pharmacogenetics in Chinese population.

    Directory of Open Access Journals (Sweden)

    Siyue Li

    Full Text Available As the most frequently prescribed anticoagulant, warfarin has large inter-individual variability in dosage. Genetic polymorphisms could largely explain the differences in dosage requirement. rs9923231 (VKORC1, rs7294 (VKORC1, rs1057910 (CYP2C9, rs2108622 (CYP4F2, and rs699664 (GGCX involved in the warfarin action mechanism and the circulatory vitamin K were selected to investigate their polymorphism characteristics and their effects on the pharmacodynamics and pharmacokinetics of warfarin in Chinese population.220 patients with cardiac valve replacement were recruited. International normalized ratio and plasma warfarin concentrations were determined. The five genetic polymorphisms were genotyping by pyro-sequencing. The relationships of maintenance dose, plasma warfarin concentration and INR were assessed among groups categorized by genotypes.rs9923231 and rs7294 in VKORC1 had the analogous genotype frequencies (D': 0.969. 158 of 220 recruited individuals had the target INR (1.5-2.5. Patients with AA of rs9923231 and CC of rs7294 required a significantly lower maintenance dose and plasma concentration than those with AG and TC, respectively. The mean weekly maintenance dose was also significantly lower in CYP2C9 rs1057910 mutated heterozygote than in patients with the wild homozygote. Eliminating the influence from environment factors (age, body weight and gender, rs9923231 and rs1057910 could explain about 32.0% of the variability in warfarin maintenance dose; rs7294 could explain 26.7% of the variability in plasma concentration. For patients with allele G of rs9923231 and allele T of rs7294, higher plasma concentration was needed to achieve the similar goal INR.A better understanding of the genetic variants in individuals can be the foundation of warfarin dosing algorithm and facilitate the reasonable and effective use of warfarin in Chinese.

  1. The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings.

    Science.gov (United States)

    Stahl, Jessica; Zessel, Katrin; Schulz, Jochen; Finke, Jan Henrik; Müller-Goymann, Christel Charlotte; Kietzmann, Manfred

    2016-04-01

    Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increases worldwide. Especially in livestock farming, large quantities of faeces contaminated with antibiotics pose a risk of the carryover of the active ingredient to the environment. Accordingly, the aim of the present study was the evaluation of the benefit of different oral dosage forms (powder, pellets, granula) in pigs concerning the environmental pollution of sulfadiazine. Two subtherapeutic dosages were evaluated in powder mixtures to gain information about their potential to pollute the pig barn. Furthermore, a new group of pigs was kept in the stable after powder feeding of another pig group to determine the possible absorption of environmentally distributed antibiotics. Pigs were orally treated with three dosage forms. Simultaneously, sedimentation and airborne dust were collected and plasma and urine levels were determined. All formulations result in comparable plasma and urine levels, but massive differences in environmental pollution (powder > pellets, granula). Pigs housing in a contaminated barn exhibit traces of sulfadiazine in plasma and urine. Using pharmaceutical formulations like pellets or granula, the environmental pollution of sulfonamides can significantly be diminished due to massive dust reduction during feeding.

  2. Suppressed Alpha Oscillations Predict Intelligibility of Speech and its Acoustic Details

    Science.gov (United States)

    Weisz, Nathan

    2012-01-01

    Modulations of human alpha oscillations (8–13 Hz) accompany many cognitive processes, but their functional role in auditory perception has proven elusive: Do oscillatory dynamics of alpha reflect acoustic details of the speech signal and are they indicative of comprehension success? Acoustically presented words were degraded in acoustic envelope and spectrum in an orthogonal design, and electroencephalogram responses in the frequency domain were analyzed in 24 participants, who rated word comprehensibility after each trial. First, the alpha power suppression during and after a degraded word depended monotonically on spectral and, to a lesser extent, envelope detail. The magnitude of this alpha suppression exhibited an additional and independent influence on later comprehension ratings. Second, source localization of alpha suppression yielded superior parietal, prefrontal, as well as anterior temporal brain areas. Third, multivariate classification of the time–frequency pattern across participants showed that patterns of late posterior alpha power allowed best for above-chance classification of word intelligibility. Results suggest that both magnitude and topography of late alpha suppression in response to single words can indicate a listener's sensitivity to acoustic features and the ability to comprehend speech under adverse listening conditions. PMID:22100354

  3. Technique-dependent decrease in thyroid absorbed dose for dental radiography

    International Nuclear Information System (INIS)

    Wood, R.E.; Bristow, R.G.; Clark, G.M.; Nussbaum, C.; Taylor, K.W.

    1989-01-01

    A LiF thermoluminescent dosimetry (TLD) system, calibrated in the tissue of interest with the beam used for experimentation, was employed to investigate dosages (muGy) to the thyroid region of an anthropomorphic phantom resultant from two dental complete-mouth radiographic procedures. Both techniques were compared in terms of dosages associated with combinations of lead apron and thyroid collar shielding while using a 70-kVp or 90-kVp x-ray beam for a 20-film complete-mouth series. Lead shielding significantly decreased the dose to the thyroid using both techniques (p less than 0.05). The use of the 90-kVp beam resulted in a significant reduction in the thyroid absorbed dose when using the bisecting angle technique (p less than 0.05) but caused a significant increase in the thyroid absorbed dose when the paralleling technique was used (p less than 0.05). The implementation of higher kilovoltage techniques in dental offices must therefore be dependent on the radiographic technique employed

  4. Length dependence of staircase potentiation: interactions with caffeine and dantrolene sodium.

    Science.gov (United States)

    Rassier, D E; MacIntosh, B R

    2000-04-01

    In skeletal muscle, there is a length dependence of staircase potentiation for which the mechanism is unclear. In this study we tested the hypothesis that abolition of this length dependence by caffeine is effected by a mechanism independent of enhanced Ca2+ release. To test this hypothesis we have used caffeine, which abolishes length dependence of potentiation, and dantrolene sodium, which inhibits Ca2+ release. In situ isometric twitch contractions of rat gastrocnemius muscle before and after 20 s of repetitive stimulation at 5 Hz were analyzed at optimal length (Lo), Lo - 10%, and Lo + 10%. Potentiation was observed to be length dependent, with an increase in developed tension (DT) of 78 +/- 12, 51 +/- 5, and 34 +/- 9% (mean +/- SEM), at Lo - 10%, Lo, and Lo + 10%, respectively. Caffeine diminished the length dependence of activation and suppressed the length dependence of staircase potentiation, giving increases in DT of 65+/-13, 53 +/- 11, and 45 +/- 12% for Lo - 10%, Lo, and Lo + 10%, respectively. Dantrolene administered after caffeine did not reverse this effect. Dantrolene alone depressed the potentiation response, but did not affect the length dependence of staircase potentiation, with increases in DT of 58 +/- 17, 26 +/- 8, and 18 +/- 7%, respectively. This study confirms that there is a length dependence of staircase potentiation in mammalian skeletal muscle which is suppressed by caffeine. Since dantrolene did not alter this suppression of the length dependence of potentiation by caffeine, it is apparently not directly modulated by Ca2+ availability in the myoplasm.

  5. Effects of maternal psychotropic drug dosage on birth outcomes

    Directory of Open Access Journals (Sweden)

    Michielsen LA

    2013-12-01

    Full Text Available Laura A Michielsen,1 Frank MMA van der Heijden,1 Paddy KC Janssen,2 Harold JH Kuijpers11Vincent van Gogh Institute for Psychiatry, Venlo, the Netherlands; 2Department of Pharmacy, VieCuri Medical Centre, Venlo, the NetherlandsBackground: The aim of this retrospective study was to explore the relationship between psychotropic medication dosage and birth outcomes.Methods: A total of 136 women were enrolled, who had an active mental disorder, were taking medication to prevent a relapse, or had a history of postpartum depression or psychosis. Medication use was evaluated for the three trimesters and during labor. Based on the defined daily dose, medication use was classified into three groups. Primary outcome variables included the infant gestational age at birth, birth weight, and Apgar scores at one and 5 minutes.Results: Our study showed a significantly higher incidence of Apgar score ≤7 at 5 minutes in women taking psychotropic drugs as compared with the group taking no medication, respectively (16.3% versus 0.0%, P=0.01. There was no significant difference between the two groups in Apgar score at one minute or in gestational age and birth weight. The results showed no significant differences in gestational age, birth weight, or Apgar scores for a low–intermediate or high dose of a selective serotonin reuptake inhibitor and for a low or intermediate dose of an antipsychotic.Conclusion: This study does not indicate a relationship between doses of selective serotonin reuptake inhibitors and antipsychotics and adverse neonatal outcomes.Keywords: pregnancy, psychotropic medication, dosage, birth outcomes

  6. Evaluating dosage effects for the positive action program: How implementation impacts internalizing symptoms, aggression, school hassles, and self-esteem.

    Science.gov (United States)

    Smokowski, Paul R; Guo, Shenyang; Wu, Qi; Evans, Caroline B R; Cotter, Katie L; Bacallao, Martica

    2016-01-01

    Positive Action (PA) is a school-based intervention for elementary-, middle-, and high-school students that aims to decrease problem behaviors (e.g., violence, substance use) and increase positive behaviors (e.g., academic achievement, school engagement). PA has a long history of documented success achieving these aims, making it an Evidence Based Practice (EBP). Intervention research on EBP's has established the importance of implementation fidelity, especially with regard to program dosage; failure to properly implement an EBP can have negative consequences on targeted outcomes, especially if participants are exposed to a low dosage of the program (e.g., fewer lessons than specified). Much of the current research on PA has neglected to examine how program dosage impacts PA's effect on targeted outcomes. Using propensity score models, multiple imputation, and a 2-level hierarchical linear model, the current study fills this gap and examines how different dosages of PA as measured by years participating in PA and number of PA lessons, impacts adolescent internalizing symptoms, aggression, perceptions of school hassles, and self-esteem over a 3-year period. The current sample included middle school students in grades 6, 7, and 8 (N = 5,894). The findings indicate that students who received 3 years of the PA intervention and a high number of PA lessons had a significantly higher self-esteem score than those who received 0 years of PA or zero lessons. Participants who received 1 year of PA also reported significantly lower school hassle scores than those who received 0 years. Dosage had no statistically significant effects on aggression or internalizing score. Implications are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. Evaluation on the influence of electrocardiograph modulated milliampere on image quality and exposure dosage of volume CT heart scan

    International Nuclear Information System (INIS)

    Zhang Sen; Du Xiangke; Li Jianyin

    2006-01-01

    Objective: To find out whether the use of ECG modulated current (mA) will influence image quality and to decide whether the electrocardiograph (ECG) modulated mA will effectively reduce the exposure dosage. Methods: The cardiac pulsating phantom was set at three speed levels, i.e. high, medium, and low speed so as to simulate different heart rates. The phantom was scanned with ECG modulated mA turned on and off, and the exposure dosage of each scan sequence was documented. The images were reconstructed with reconstruction algorithm that matched the different levels of heart rate. CT values and their corresponding standard deviations at uniform areas on the images and the variation of the CT values at different locations were measured. The results from the two groups with and without ECG modulated mA were analyzed. Results: Under the same level of heart rate, the exposure dosage was remarkably reduced when the ECG modulated mA was on than when it was off. Statistical analysis showed no significant difference (P>0.05) between the images from the two groups. Conclusion: When scanning the heart with volume CT (VCT), the application of ECG modulated mA can effectively reduce the exposure dosage without sacrificing the image quality. (authors)

  8. Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

    Directory of Open Access Journals (Sweden)

    Zorica Djurić

    2012-10-01

    Full Text Available Implementation of the Quality by Design (QbD approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

  9. Feasibility study on low-dosage digital tomosynthesis (DTS) using a multislit collimation technique

    Science.gov (United States)

    Park, S. Y.; Kim, G. A.; Park, C. K.; Cho, H. S.; Seo, C. W.; Lee, D. Y.; Kang, S. Y.; Kim, K. S.; Lim, H. W.; Lee, H. W.; Park, J. E.; Kim, W. S.; Jeon, D. H.; Woo, T. H.

    2018-04-01

    In this study, we investigated an effective low-dose digital tomosynthesis (DTS) where a multislit collimator placed between the X-ray tube and the patient oscillates during projection data acquisition, partially blocking the X-ray beam to the patient thereby reducing the radiation dosage. We performed a simulation using the proposed DTS with two sets of multislit collimators both having a 50% duty cycle and investigated the image characteristics to demonstrate the feasibility of this proposed approach. In the simulation, all projections were taken at a tomographic angle of θ = ± 50° and an angle step of Δθ =2°. We utilized an iterative algorithm based on a compressed-sensing (CS) scheme for more accurate DTS reconstruction. Using the proposed DTS, we successfully obtained CS-reconstructed DTS images with no bright-band artifacts around the multislit edges of the collimator, thus maintaining the image quality. Therefore, the use of multislit collimation in current real-world DTS systems can reduce the radiation dosage to patients.

  10. Colour Terms Affect Detection of Colour and Colour-Associated Objects Suppressed from Visual Awareness

    OpenAIRE

    Forder, Lewis; Taylor, Olivia; Mankin, Helen; Scott, Ryan B.; Franklin, Anna

    2016-01-01

    The idea that language can affect how we see the world continues to create controversy. A potentially important study in this field has shown that when an object is suppressed from visual awareness using continuous flash suppression (a form of binocular rivalry), detection of the object is differently affected by a preceding word prime depending on whether the prime matches or does not match the object. This may suggest that language can affect early stages of vision. We replicated this parad...

  11. Prediction of required ozone dosage for pilot recirculating aquaculture systems based on laboratory studies

    DEFF Research Database (Denmark)

    Spiliotopoulou, Aikaterini; Rojas-Tirado, Paula Andrea; Kaarsholm, Kamilla Marie Speht

    2017-01-01

    In recirculating aquaculture systems (RAS), the water quality changes continuously. Organic and inorganic compounds accumulates creating toxic conditions for the farmed organisms. Ozone improves water quality diminishing significantly both bacteria load and dissolved organic matter. However......, in a non-meticulously designed system, residual ozone might reach the culture tanks causing significant harm to cultured species or excess costs. The aim of the study was to predict the suitable ozone dosage in pilot RAS, for water treatment purposes, based on laboratory studies. The ozone effect on water...... quality of freshwater RAS and system’s ozone demand was investigated. Bench-scale ozonation experiments revealed the ozone demand of the system to be 180 mg O3/h. Three different ozone dosages were applied to four replicated systems with fixed feed loading (1.56 kg feed/m3 make up water). Results...

  12. Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality.

    Science.gov (United States)

    Içten, Elçin; Giridhar, Arun; Nagy, Zoltan K; Reklaitis, Gintaras V

    2016-04-01

    The features of a drop-on-demand-based system developed for the manufacture of melt-based pharmaceuticals have been previously reported. In this paper, a supervisory control system, which is designed to ensure reproducible production of high quality of melt-based solid oral dosages, is presented. This control system enables the production of individual dosage forms with the desired critical quality attributes: amount of active ingredient and drug morphology by monitoring and controlling critical process parameters, such as drop size and product and process temperatures. The effects of these process parameters on the final product quality are investigated, and the properties of the produced dosage forms characterized using various techniques, such as Raman spectroscopy, optical microscopy, and dissolution testing. A crystallization temperature control strategy, including controlled temperature cycles, is presented to tailor the crystallization behavior of drug deposits and to achieve consistent drug morphology. This control strategy can be used to achieve the desired bioavailability of the drug by mitigating variations in the dissolution profiles. The supervisor control strategy enables the application of the drop-on-demand system to the production of individualized dosage required for personalized drug regimens.

  13. [National and regional market penetration rates of generic's high dosage buprenorphine: its evolution from 2006 to 2008, using reimbursed drug database].

    Science.gov (United States)

    Boczek, Christelle; Frauger, Elisabeth; Micallef, Joëlle; Allaria-Lapierre, Véronique; Reggio, Patrick; Sciortino, Vincent

    2012-01-01

    To assess the national market penetration rate (PR) of generic high-dosage buprenorphine (HDB) in 2008 and its evolution since their marketing (2006), and making a point for each dosage and at regional level. Retrospective study over data using national and regional health reimbursement database over three years (2006-2008). In 2008, the generic HDB's national MPR was 31%. The PR for each dosage were 45% for 0.4 mg, 36% for 2 mg and 19% for 8 mg. The (PR) based on Defined Daily Dose (DDD) was 23% in 2008, 15% in 2007 and 4% in 2006. In 2008, at the regional level, disparities were observed in the adjusted penetration rate from 15% in Île de France to 39% in Champagne Ardennes Lorraine. The national PR of generic HDB has increased. There are differences in MPR in terms of dosage and area. However, this PR is still low (in 2008, 82% of the delivered drugs are generics). © 2012 Société Française de Pharmacologie et de Thérapeutique.

  14. The influences of adrenaline dosing frequency and dosage on outcomes of adult in-hospital cardiac arrest: A retrospective cohort study.

    Science.gov (United States)

    Wang, Chih-Hung; Huang, Chien-Hua; Chang, Wei-Tien; Tsai, Min-Shan; Yu, Ping-Hsun; Wu, Yen-Wen; Hung, Kuan-Yu; Chen, Wen-Jone

    2016-06-01

    To investigate the influence of dosing frequency and dosage of adrenaline on outcomes of cardiopulmonary resuscitation (CPR). We conducted a retrospective observational study in a single medical centre and included adult patients who had suffered an in-hospital cardiac arrest between 2006 and 2012. We used multivariable logistic regression analysis to evaluate the associations between independent variables and outcomes. Adrenaline average dosing frequency was calculated as the total dosage of adrenaline administered during CPR divided by the duration of CPR. Body weight (BW) was analysed as an interaction term to investigate the effect of adrenaline dosage on outcomes. Favourable neurological outcome was defined as a score of 1 or 2 on the Cerebral Performance Category scale at hospital discharge. We included 896 patients in the analysis. After adjusting for multiple confounding factors, including CPR duration, the results indicated that higher adrenaline dosing frequency was associated with lower rates of survival (odds ratio (OR): 0.05, 95% confidence interval (CI): 0.01-0.23) and favourable neurological outcome at hospital discharge (OR: 0.02, 95% CI: 0.002-0.16). A significant interaction was noted between total adrenaline dosage and BW, which indicated that, with the same adrenaline dosage, the outcomes for patients with BW≥82.5kg would be worse than those for patients with lower BW. Higher adrenaline average dosing frequency may be associated with worse outcomes after CPR. Besides, according to current recommendations, patients with BW above 82.5kg may not receive adequate dose of adrenaline. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Spironolactone induces apoptosis in human mononuclear cells. Association between apoptosis and cytokine suppression

    DEFF Research Database (Denmark)

    Mikkelsen, Martin; Sønder, S U; Nersting, J

    2006-01-01

    Spironolactone (SPIR) has been described to suppress accumulation of pro-inflammatory cytokines. Here, the suppression of TNF-alpha in lipopolysaccharide (LPS)-stimulated mononuclear cell cultures was confirmed. However, SPIR was also found to induce apoptosis, prompting the investigations...... of a possible association between the two effects: The apoptosis-inducing and the cytokine-suppressive effects of SPIR correlated with regard to the effective concentration range. Also, pre-incubation experiments demonstrated a temporal separation of the two effects of ... preceding apoptosis. An association between the two effects was also seen when testing several SPIR analogues. Contrary to TNF-alpha, the levels of IL-1beta increased in SPIR-treated cultures. However, the amount of IL-1beta in the supernatants depended upon the order of SPIR and LPS addition, as IL-1beta...

  16. 76 FR 3488 - Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin

    Science.gov (United States)

    2011-01-20

    .... FDA-2010-N-0002] Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline and Flunixin... combination drug injectable solution containing oxytetracycline and flunixin meglumine in cattle. [[Page 3489... veterinary prescription use of HEXASOL (oxytetracycline and flunixin meglumine) Injection for the treatment...

  17. Dropwise additive manufacturing of pharmaceutical products for melt-based dosage forms.

    Science.gov (United States)

    Içten, Elçin; Giridhar, Arun; Taylor, Lynne S; Nagy, Zoltan K; Reklaitis, Gintaras V

    2015-05-01

    The US Food and Drug Administration introduced the quality by design approach and process analytical technology guidance to encourage innovation and efficiency in pharmaceutical development, manufacturing, and quality assurance. As part of this renewed emphasis on the improvement of manufacturing, the pharmaceutical industry has begun to develop more efficient production processes with more intensive use of online measurement and sensing, real-time quality control, and process control tools. Here, we present dropwise additive manufacturing of pharmaceutical products (DAMPP) as an alternative to conventional pharmaceutical manufacturing methods. This mini-manufacturing process for the production of pharmaceuticals utilizes drop on demand printing technology for automated and controlled deposition of melt-based formulations onto edible substrates. The advantages of drop-on-demand technology, including reproducible production of small droplets, adjustable drop sizing, high placement accuracy, and flexible use of different formulations, enable production of individualized dosing even for low-dose and high-potency drugs. In this work, DAMPP is used to produce solid oral dosage forms from hot melts of an active pharmaceutical ingredient and a polymer. The dosage forms are analyzed to show the reproducibility of dosing and the dissolution behavior of different formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  18. Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.

    Science.gov (United States)

    Hofsäss, Martin A; Souza, Jacqueline de; Silva-Barcellos, Neila M; Bellavinha, Karime R; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Parr, Alan; Langguth, Peter; Polli, James E; Shah, Vinod P; Tajiri, Tomokazu; Mehta, Mehul U; Dressman, Jennifer B

    2017-12-01

    This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data for higher doses of 1-5 mg are inconclusive. Following a conservative approach, folic acid is classified as a Biopharmaceutics Classification System class IV compound until more reliable data become available. Commensurate with its solubility characteristics, the results of dissolution studies indicated that none of the folic acid products evaluated showed rapid dissolution in media at pH 1.2 or 4.5. Therefore, according to the current criteria of the Biopharmaceutics Classification System, the biowaiver approval procedure cannot be recommended for immediate-release solid oral dosage forms containing folic acid. Copyright © 2017 American Pharmacists Association®. All rights reserved.

  19. TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients

    Science.gov (United States)

    Caceres, Gisela; McGraw, Kathy; Yip, Bon Ham; Pellagatti, Andrea; Johnson, Joseph; Zhang, Ling; Liu, Kenian; Zhang, Lan Min; Fulp, William J.; Lee, Ji-Hyun; Al Ali, Najla H.; Basiorka, Ashley; Smith, Larry J.; Daugherty, F. Joseph; Littleton, Neil; Wells, Richard A.; Sokol, Lubomir; Wei, Sheng; Komrokji, Rami S.; Boultwood, Jacqueline; List, Alan F.

    2013-01-01

    Stabilization of p53 in erythroid precursors in response to nucleosomal stress underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically active 20-mer antisense oligonucleotide complementary to TP53 exon10, could suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced cellular p53 and p53-up-regulated modulator of apoptosis expression compared with controls, accompanied by a significant reduction in apoptosis and increased cell proliferation. In a two-stage erythroid differentiation assay, cenersen significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from patients with del(5q) MDS, whereas erythroid burst recovery increased proportionally to the magnitude of p53 suppression without evidence of del(5q) clonal suppression (r = −0.6; P = 0.005). To explore the effect of p53 suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor-dependent p53 antagonist, was added to lenalidomide treatment in eight lower-risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance. Transfusion independence was restored in five patients accompanied by expansion of erythroid precursors and decreased cellular p53 expression. We conclude that targeted suppression of p53 could support effective erythropoiesis in lenalidomide-resistant del(5q) MDS. PMID:24043769

  20. The rhizosphere microbial community in a multiple parallel mineralization system suppresses the pathogenic fungus Fusarium oxysporum

    Science.gov (United States)

    Fujiwara, Kazuki; Iida, Yuichiro; Iwai, Takashi; Aoyama, Chihiro; Inukai, Ryuya; Ando, Akinori; Ogawa, Jun; Ohnishi, Jun; Terami, Fumihiro; Takano, Masao; Shinohara, Makoto

    2013-01-01

    The rhizosphere microbial community in a hydroponics system with multiple parallel mineralization (MPM) can potentially suppress root-borne diseases. This study focused on revealing the biological nature of the suppression against Fusarium wilt disease, which is caused by the fungus Fusarium oxysporum, and describing the factors that may influence the fungal pathogen in the MPM system. We demonstrated that the rhizosphere microbiota that developed in the MPM system could suppress Fusarium wilt disease under in vitro and greenhouse conditions. The microbiological characteristics of the MPM system were able to control the population dynamics of F. oxysporum, but did not eradicate the fungal pathogen. The roles of the microbiological agents underlying the disease suppression and the magnitude of the disease suppression in the MPM system appear to depend on the microbial density. F. oxysporum that survived in the MPM system formed chlamydospores when exposed to the rhizosphere microbiota. These results suggest that the microbiota suppresses proliferation of F. oxysporum by controlling the pathogen's morphogenesis and by developing an ecosystem that permits coexistence with F. oxysporum. PMID:24311557

  1. Effectiveness of several dosage formula of oil and nano emulsion of citronella against vascular streak dieback (VSD) disease on cocoa

    Science.gov (United States)

    Noveriza, R.; Trisno, J.; Rahma, H.; Yuliani, S.; Reflin; Martinius

    2018-02-01

    The disease of Vascular streak dieback (VSD) is a deadly disease of cocoa plants, because it attacks the vascular tissue of cocoa at growing point of the plant. In West Sumatra the disease was first reported in 2015 with an incidence of disease range 58.82% - 100% and an intensity of disease range 24.29% - 44.7%. The purpose of this study was to examine the effectiveness of dosage application of oil formula and nano emulsion of citronella formula against Vascular streak dieback (VSD) disease on cocoa plants in West Sumatra (in Padang Pariaman District and Limapuluh Kota District). The results showed that the percentage of VSD disease attacks in both testing sites was 100%. The oil and nano emulsion of citronella formulas can reduce the intensity of VSD disease on cocoa plants in West Sumatra, particularly in Padang Pariaman District and Limapuluh Kota District. The reduction of VSD intensity in Padang Pariaman district ranged from 8.32 to 21.13%; while in Limapuluh Kota district ranged from 4.33 to 11.80%. The nano emulsion of citronella formulation is effective to suppress the intensity of VSD disease on cocoa plants at doses 0.1% (≥ 30% of effectiveness level).

  2. Suppression of neutrophil accumulation in mice by cutaneous application of geranium essential oil

    Directory of Open Access Journals (Sweden)

    Oshima Haruyuki

    2005-02-01

    Full Text Available Abstract Background Previous studies suggested that essential oils suppressed the adherence response of human neutrophils in vitro and that intraperitoneal application of geranium oil suppressed the neutrophil accumulation into peritoneal cavity in vivo. Usually, essential oils are applied through skin in aromatherapy in inflammatory symptoms. The purpose of this study is to assess the effects of cutaneous application of essential oils on the accumulation of neutrophils in inflammatory sites in skin of mice. Methods Inflammation with accumulation of inflammatory cells was induced by injection of curdlan, a (1→3-β-D-glucan in skin or peritoneal cavity of mice. Essential oils were applied cutaneously to the mice immediately and 3 hr after intradermal injection of curdlan. The skin with inflammatory lesion was cut off 6 hr after injection of curdlan, and the homogenates were used for myeloperoxidase (MPO: a marker enzyme of neutrophil granule assay. Results The MPO activity of the skin lesion induced by curdlan was suppressed dose-dependently by cutaneous application of geranium oil. Other oils such as lavender, eucalyptus and tea tree oils also suppressed the activity, but their activities seemed weaker than geranium. Juniper oil didn't suppress the activity Conclusion Cutaneous application of essential oils, especially geranium oil, can suppress the inflammatory symptoms with neutrophil accumulation and edema.

  3. Transmission microscopy of unmodified biological materials: comparative radiation dosages with electrons and ultrasoft X-ray photons

    International Nuclear Information System (INIS)

    Sayre, D.; Feder, R.; Spiller, E.; Kirz, J.; Kim, D.M.

    1977-01-01

    The minimum radiation dosage in a specimen consistent with transmission microscopy at resolution d and specimen thickness t is calculated for model specimens resembling biological materials in their natural state. The calculations cover 10 4 -10 7 eV electrons and 1.3-90 A photons in a number of microscopy modes. The results indicate that over a considerable part of the (t,d)-plane transmission microscopy on such specimens can be carried out at lower dosage with photons than with electrons. Estimates of the maximum resolutions obtainable with electrons and photons, consistent with structural survival of the specimen, are obtained, as are data on optimal operating conditions for microscopy with the two particles

  4. Degree of Suppression of Mouse Myoblast Cell Line C₂C12 Differentiation Varies According to Chondroitin Sulfate Subtype.

    Science.gov (United States)

    Warita, Katsuhiko; Oshima, Nana; Takeda-Okuda, Naoko; Tamura, Jun-Ichi; Hosaka, Yoshinao Z

    2016-10-21

    Chondroitin sulfate (CS), a type of glycosaminoglycan (GAG), is a factor involved in the suppression of myogenic differentiation. CS comprises two repeating sugars and has different subtypes depending on the position and number of bonded sulfate groups. However, the effect of each subtype on myogenic differentiation remains unclear. In this study, we spiked cultures of C₂C 12 myoblasts, cells which are capable of undergoing skeletal muscle differentiation, with one of five types of CS (CS-A, -B, -C, -D, or -E) and induced differentiation over a fixed time. After immunostaining of the formed myotubes with an anti-MHC antibody, we counted the number of nuclei in the myotubes and then calculated the fusion index (FI) as a measure of myotube differentiation. The FI values of all the CS-treated groups were lower than the FI value of the control group, especially the group treated with CS-E, which displayed notable suppression of myotube formation. To confirm that the sugar chain in CS-E is important in the suppression of differentiation, chondroitinase ABC (ChABC), which catabolizes CS, was added to the media. The addition of ChABC led to the degradation of CS-E, and neutralized the suppression of myotube formation by CS-E. Collectively, it can be concluded that the degree of suppression of differentiation depends on the subtype of CS and that CS-E strongly suppresses myogenic differentiation. We conclude that the CS sugar chain has inhibitory action against myoblast cell fusion.

  5. Demonstration of suppressed phonon tunneling losses in phononic bandgap shielded membrane resonators for high-Q optomechanics.

    Science.gov (United States)

    Tsaturyan, Yeghishe; Barg, Andreas; Simonsen, Anders; Villanueva, Luis Guillermo; Schmid, Silvan; Schliesser, Albert; Polzik, Eugene S

    2014-03-24

    Dielectric membranes with exceptional mechanical and optical properties present one of the most promising platforms in quantum opto-mechanics. The performance of stressed silicon nitride nanomembranes as mechanical resonators notoriously depends on how their frame is clamped to the sample mount, which in practice usually necessitates delicate, and difficult-to-reproduce mounting solutions. Here, we demonstrate that a phononic bandgap shield integrated in the membrane's silicon frame eliminates this dependence, by suppressing dissipation through phonon tunneling. We dry-etch the membrane's frame so that it assumes the form of a cm-sized bridge featuring a 1-dimensional periodic pattern, whose phononic density of states is tailored to exhibit one, or several, full band gaps around the membrane's high-Q modes in the MHz-range. We quantify the effectiveness of this phononic bandgap shield by optical interferometry measuring both the suppressed transmission of vibrations, as well as the influence of frame clamping conditions on the membrane modes. We find suppressions up to 40 dB and, for three different realized phononic structures, consistently observe significant suppression of the dependence of the membrane's modes on sample clamping-if the mode's frequency lies in the bandgap. As a result, we achieve membrane mode quality factors of 5 × 10(6) with samples that are tightly bolted to the 8 K-cold finger of a cryostat. Q × f -products of 6 × 10(12) Hz at 300 K and 14 × 10(12) Hz at 8 K are observed, satisfying one of the main requirements for optical cooling of mechanical vibrations to their quantum ground-state.

  6. Symptomless endophytic fungi suppress endogenous levels of salicylic acid and interact with the jasmonate-dependent indirect defense traits of their host, lima bean (Phaseolus lunatus).

    Science.gov (United States)

    Navarro-Meléndez, Ariana L; Heil, Martin

    2014-07-01

    Symptomless ‘type II’ fungal endophytes colonize their plant host horizontally and exert diverse effects on its resistance phenotype. Here, we used wild Lima bean (Phaseolus lunatus) plants that were experimentally colonized with one of three strains of natural endophytes (Bartalinia pondoensis, Fusarium sp., or Cochliobolus lunatus) to investigate the effects of fungal colonization on the endogenous levels of salicylic acid (SA) and jasmonic acid (JA) and on two JA-dependent indirect defense traits. Colonization with Fusarium sp. enhanced JA levels in intact leaves, whereas B. pondoensis suppressed the induction of endogenous JA in mechanically damaged leaves. Endogenous SA levels in intact leaves were significantly decreased by all strains and B. pondoensis and Fusarium sp. decreased SA levels after mechanical damage. Colonization with Fusarium sp. or C. lunatus enhanced the number of detectable volatile organic compounds (VOCs) emitted from intact leaves, and all three strains enhanced the relative amount of several VOCs emitted from intact leaves as well as the number of detectable VOCs emitted from slightly damaged leaves. All three strains completely suppressed the induced secretion of extrafloral nectar (EFN) after the exogenous application of JA. Symptomless endophytes interact in complex and strain-specific ways with the endogenous levels of SA and JA and with the defense traits that are controlled by these hormones. These interactions can occur both upstream and downstream of the defense hormones.

  7. Suppression of NRF2–ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells

    International Nuclear Information System (INIS)

    Peng, Hui; Wang, Huihui; Xue, Peng; Hou, Yongyong; Dong, Jian; Zhou, Tong; Qu, Weidong; Peng, Shuangqing; Li, Jin; Carmichael, Paul L.; Nelson, Bud; Clewell, Rebecca; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2016-01-01

    Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chemical detoxification in normal and tumor cells. Consistent with previous findings that NRF2–ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As 2 O 3 ), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2–ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As 2 O 3 -challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2–ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As 2 O 3 -induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As 2 O 3 -induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2–ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents. - Highlights: • Identification of novel inhibitors of ARE-dependent transcription • Suppression of NRF2–ARE sensitizes THP-1 cells to chemotherapy. • Ethionamide suppresses ARE-dependent transcriptional activity. • Ethionamide and isoniazid increase the cytotoxicity of As 2 O 3 in AML cells. • Sensitization of THP-1 cells to As 2 O 3 toxicity by ethionamide is NRF2-dependent.

  8. Pressure suppressing device

    International Nuclear Information System (INIS)

    Naito, Makoto.

    1980-01-01

    Purpose: To prevent the pressure in the reactor container from excessively increasing even when vapor leaks from the dry well to a space of the suppression chamber, without passing though the suppression pool at the time of loss of coolant accident. Constitution: When vapor of a high temperature and a high pressure at the time of loss of coolant accident flows from the dry well to the suppression chamber without passing through suppression pool water, vapor dose not condense with pool water, and therefore the pressure within the chamber abnormally increases. For this reason, this abnormal pressure is detected by a pressure detector thereby to start the operations of a blower and a pump. By starting the blower, the pressure in the dry well becomes lower than the pressure in the chamber, and vapor entirely passes through the pool water and entirely condenses with the pool water. By starting the pump, the pool water is sprayed over the space of the chamber, and vapor in the space is condensed. (Yoshino, Y.)

  9. Protective effect of Lycium Barbarum polysaccharides on dextromethorphan-induced mood impairment and neurogenesis suppression.

    Science.gov (United States)

    Po, Kevin Kai-Ting; Leung, Joseph Wai-Hin; Chan, Jackie Ngai-Man; Fung, Timothy Kai-Hang; Sánchez-Vidaña, Dalinda Isabel; Sin, Emily Lok-Lam; So, Kwok-Fai; Lau, Benson Wui-Man; Siu, Andrew Man-Hong

    2017-09-01

    Dextromethorphan (DXM) is one of the common drugs abused by adolescents. It is the active ingredient found in cough medicine which is used for suppressing cough. High dosage of DXM can induce euphoria, dissociative effects and even hallucinations. Chronic use of DXM may also lead to depressive-related symptoms. Lycium barbarum, commonly known as wolfberry, has been used as a traditional Chinese medicine for the treatment of ageing-related neurodegenerative diseases. A recent study has shown the potential beneficial effect of Lycium barbarum to reduce depression-like behavior. In the present study, we investigated the role of Lycium barbarum polysaccharide (LBP) to alleviate DXM-induced emotional distress. Sprague Dawley rats were divided into 4 groups (n=6 per group), including the normal control (vehicles only), DXM-treated group (40 mg/kg DXM), LBP-treated group (1 mg/kg LBP) and DXM+ LBP-treated group (40 mg/kg DXM and 1 mg/kg LBP). After two-week treatment, the DXM-treated group showed increased depression-like and social anxiety-like behaviors in the forced swim test and social interaction test respectively. On the other hand, the adverse behavioral effects induced by DXM were reduced by LBP treatment. Histological results showed that LBP treatment alone did not promote hippocampal neurogenesis when compared to the normal control, but LBP could lessen the suppression of hippocampal neurogenesis induced by DXM. The findings provide insights for the potential use of wolfberry as an adjunct treatment option for alleviating mood disturbances during rehabilitation of cough syrup abusers. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Assessment of Digoxin-Specific Fab Fragment Dosages in Digoxin Poisoning.

    Science.gov (United States)

    Nordt, Sean Patrick; Clark, Richard F; Machado, Carol; Cantrell, F Lee

    2016-01-01

    Digoxin poisoning still remains a common cause of morbidity and mortality. Fortunately, digoxin-specific Fab fragments are commercially available as an antidote. However, these Fab fragments are several thousand dollars per vial. There is a standardized formula to calculate appropriate Fab fragment dosage based on the serum digoxin concentration. This can greatly reduce the amount of Fab fragment administered. There is also an empiric dosing guideline recommending 6-10 vials be given; however, this may result in higher amounts of Fab fragments being administered than required. We performed this study to assess the amounts of digoxin-specific Fab fragments administered in the treatment of digoxin poisonings recorded in a poison control system database from January 1, 2000, to December 31, 2009, in which digoxin serum concentrations were available. This was a retrospective study of 278 patients, 107 with acute poisonings (group A) and 171 following chronic poisoning (group B). In group A, the calculated Fab dose was higher than the calculated dose based on available concentrations in 39 (36%) of group A and 15 (9%) of group B patients. The average wholesale price cost of the excessive dosages ranged from $4818 to as high as $50,589 per patient. Our data suggests that clinician education on digoxin poisoning and the use of the standardized formula to calculate the Fab dose may decrease over utilization and decrease costs associated with the administration of digoxin-specific Fab fragments in the treatment of digoxin poisonings.

  11. The role of suppression in amblyopia.

    Science.gov (United States)

    Li, Jingrong; Thompson, Benjamin; Lam, Carly S Y; Deng, Daming; Chan, Lily Y L; Maehara, Goro; Woo, George C; Yu, Minbin; Hess, Robert F

    2011-06-13

    This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

  12. Testosterone suppression of CRH-stimulated cortisol in men.

    Science.gov (United States)

    Rubinow, David R; Roca, Catherine A; Schmidt, Peter J; Danaceau, Merry A; Putnam, Karen; Cizza, Giovanni; Chrousos, George; Nieman, Lynnette

    2005-10-01

    Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in 10 men (ages 18-45 years) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (pcortisol area under the curve was lower at a trend level (pcortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (pcortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone.

  13. Distinguishing among potential mechanisms of singleton suppression.

    Science.gov (United States)

    Gaspelin, Nicholas; Luck, Steven J

    2018-04-01

    Previous research has revealed that people can suppress salient stimuli that might otherwise capture visual attention. The present study tests between 3 possible mechanisms of visual suppression. According to first-order feature suppression models , items are suppressed on the basis of simple feature values. According to second-order feature suppression models , items are suppressed on the basis of local discontinuities within a given feature dimension. According to global-salience suppression models , items are suppressed on the basis of their dimension-independent salience levels. The current study distinguished among these models by varying the predictability of the singleton color value. If items are suppressed by virtue of salience alone, then it should not matter whether the singleton color is predictable. However, evidence from probe processing and eye movements indicated that suppression is possible only when the color values are predictable. Moreover, the ability to suppress salient items developed gradually as participants gained experience with the feature that defined the salient distractor. These results are consistent with first-order feature suppression models, and are inconsistent with the other models of suppression. In other words, people primarily suppress salient distractors on the basis of their simple features and not on the basis of salience per se. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity

    Directory of Open Access Journals (Sweden)

    Masako Isokawa

    2016-01-01

    Full Text Available GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing [Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition, mediated by endogenous cannabinoids that require a [Ca2+]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI persisted in the absence of a [Ca2+]i rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust Ca2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.

  15. Design of a gastroretentive mucoadhesive dosage form of furosemide for controlled release

    Directory of Open Access Journals (Sweden)

    Sharad S. Darandale

    2012-10-01

    Full Text Available The aim of the present study was to develop and characterize a gastroretentive dosage form suitable for controlled drug release. It consists of a drug loaded polymeric film made up of a bilayer of immediate (IR and controlled release (CR layers folded into a hard gelatin capsule. Gastroretention results from unfolding and swelling of the film and its bioadhesion to the gastric mucosa. Furosemide, a drug with a narrow absorption window, was selected as the model drug. Inclusion of hydroxypropyl β-cyclodextrin in both layers and Carbopol® 971P NF in the CR layer of the bilayer film resulted in optimum drug release, bioadhesion and mechanical properties. The film with zig-zag folding in the capsule was shown to unfold and swell under acidic conditions and provide IR of drug over 1 h and CR for up to 12 h in acidic medium. X-ray diffraction, differential scanning calorimetry and scanning electron microscopy revealed uniform dispersion of furosemide in the polymeric matrices. The results indicate the dosage form is gastroretentive and can provide controlled release of drugs with narrow therapeutic windows.

  16. Dosage effect of a Phex mutation in a murine model of X-linked hypophosphatemia

    Science.gov (United States)

    Ichikawa, Shoji; Gray, Amie K.; Bikorimana, Emmanuel; Econs, Michael J.

    2013-01-01

    X-linked hypophosphatemia (XLH) is caused by mutations in the PHEX gene, which increase circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Since XLH is a dominant disease, one mutant allele is sufficient for manifestation of the disease. However, dosage effect of a PHEX mutation in XLH is not completely understood. To examine the effect of Phex genotypes, we compared serum biochemistries and skeletal measures between all five possible genotypes of a new murine model of XLH (PhexK496X or PhexJrt). Compared to sex-matched littermate controls, all Phex mutant mice had hypophosphatemia, mild hypocalcemia, and increased parathyroid hormone and alkaline phosphatase levels. Furthermore, mutant mice had markedly elevated serum Fgf23 levels due to increased Fgf23 expression and reduced cleavage of Fgf23. Although females with a homozygous Phex mutation were slightly more hypocalcemic and hypophosphatemic than heterozygous females, the two groups had comparable intact Fgf23 levels. Similarly, there was no difference in intact Fgf23 or phosphorus concentrations between hemizygous males and heterozygous females. Compared to heterozygous females, homozygous counterparts were significantly smaller and had shorter femurs with reduced bone mineral density, suggesting the existence of dosage effect in the skeletal phenotype of XLH. However, overall phenotypic trends in regards to mineral ion homeostasis were mostly unaffected by the presence of one or two mutant Phex allele(s). The lack of gene dosage effect on circulating Fgf23 (and thus, phosphorus) levels suggests that a Phex mutation may create the lower set point for extracellular phosphate concentrations. PMID:23700148

  17. How can we model selectively neutral density dependence in evolutionary games.

    Science.gov (United States)

    Argasinski, Krzysztof; Kozłowski, Jan

    2008-03-01

    The problem of density dependence appears in all approaches to the modelling of population dynamics. It is pertinent to classic models (i.e., Lotka-Volterra's), and also population genetics and game theoretical models related to the replicator dynamics. There is no density dependence in the classic formulation of replicator dynamics, which means that population size may grow to infinity. Therefore the question arises: How is unlimited population growth suppressed in frequency-dependent models? Two categories of solutions can be found in the literature. In the first, replicator dynamics is independent of background fitness. In the second type of solution, a multiplicative suppression coefficient is used, as in a logistic equation. Both approaches have disadvantages. The first one is incompatible with the methods of life history theory and basic probabilistic intuitions. The logistic type of suppression of per capita growth rate stops trajectories of selection when population size reaches the maximal value (carrying capacity); hence this method does not satisfy selective neutrality. To overcome these difficulties, we must explicitly consider turn-over of individuals dependent on mortality rate. This new approach leads to two interesting predictions. First, the equilibrium value of population size is lower than carrying capacity and depends on the mortality rate. Second, although the phase portrait of selection trajectories is the same as in density-independent replicator dynamics, pace of selection slows down when population size approaches equilibrium, and then remains constant and dependent on the rate of turn-over of individuals.

  18. A simple spectrophotometric determination of diclofenac sodium in commercial dosage forms using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)

    International Nuclear Information System (INIS)

    Raza, A.; Ansari, T.M.; Niazi, S.B.; Bukhari, S.I.H.

    2005-01-01

    A rapid, simple and sensitive spectrophotometric method has been developed for the determination of diclofenac sodium in pure and tablet formulations. The method depends on the charge-transfer complexation between diclofenac sodium as n-electron donor with 2,3-dichloro-,6-dicyano-1,4-benzoquinone (DDQ) in acetonitrile medium as pi-acceptor to give a colored complex which absorbs maximally at 545 nm. Beer's law has been obeyed in the concentration range of 13-275 micro gram ml/sup -1/ with molar absorptivity of 2.5 x 10/sup 3/L mole/sup -1/cm/sup -1/. The proposed method is precise, accurate and specific for routine quantitative analysis of the drug in bulk and dosage forms. (author)

  19. Gene dosage, expression, and ontology analysis identifies driver genes in the carcinogenesis and chemoradioresistance of cervical cancer.

    Directory of Open Access Journals (Sweden)

    Malin Lando

    2009-11-01

    Full Text Available Integrative analysis of gene dosage, expression, and ontology (GO data was performed to discover driver genes in the carcinogenesis and chemoradioresistance of cervical cancers. Gene dosage and expression profiles of 102 locally advanced cervical cancers were generated by microarray techniques. Fifty-two of these patients were also analyzed with the Illumina expression method to confirm the gene expression results. An independent cohort of 41 patients was used for validation of gene expressions associated with clinical outcome. Statistical analysis identified 29 recurrent gains and losses and 3 losses (on 3p, 13q, 21q associated with poor outcome after chemoradiotherapy. The intratumor heterogeneity, assessed from the gene dosage profiles, was low for these alterations, showing that they had emerged prior to many other alterations and probably were early events in carcinogenesis. Integration of the alterations with gene expression and GO data identified genes that were regulated by the alterations and revealed five biological processes that were significantly overrepresented among the affected genes: apoptosis, metabolism, macromolecule localization, translation, and transcription. Four genes on 3p (RYBP, GBE1 and 13q (FAM48A, MED4 correlated with outcome at both the gene dosage and expression level and were satisfactorily validated in the independent cohort. These integrated analyses yielded 57 candidate drivers of 24 genetic events, including novel loci responsible for chemoradioresistance. Further mapping of the connections among genetic events, drivers, and biological processes suggested that each individual event stimulates specific processes in carcinogenesis through the coordinated control of multiple genes. The present results may provide novel therapeutic opportunities of both early and advanced stage cervical cancers.

  20. GNOSIS: THE FIRST INSTRUMENT TO USE FIBER BRAGG GRATINGS FOR OH SUPPRESSION

    Energy Technology Data Exchange (ETDEWEB)

    Trinh, Christopher Q.; Ellis, Simon C.; Bland-Hawthorn, Joss; Bryant, Julia; O' Byrne, John [Sydney Institute for Astronomy, School of Physics, The University of Sydney, NSW 2006 (Australia); Lawrence, Jon S.; Horton, Anthony J.; Shortridge, Keith; Case, Scott; Colless, Matthew; Gers, Luke; Lee, Steve; Miziarski, Stan [Australian Astronomical Observatory, 105 Delhi Road, North Ryde, P.O. Box 915, NSW 1670 (Australia); Leon-Saval, Sergio G. [Institute of Photonics and Optical Science, School of Physics, University of Sydney, NSW 2006 (Australia); Couch, Warrick; Glazebrook, Karl [Centre for Astrophysics and Supercomputing, Swinburne University of Technology, P.O. Box 218, Hawthorn, VIC 3122 (Australia); Freeman, Kenneth [Research School of Astronomy and Astrophysics, Australian National University, Weston Creek, ACT 2611 (Australia); Loehmannsroeben, Hans-Gerd [innoFSPEC-Institut fuer Chemie/Physikalische Chemie, Universitaet Potsdam, Karl-Liebknecht-Strasse 24-25, D-14476 Potsdam-Golm (Germany); Haynes, Roger; Roth, Martin M., E-mail: c.trinh@physics.usyd.edu.au [innoFSPEC-Leibniz-Institut fuer Astrophysik Potsdam, An der Sternwarte 16, D-14482 Potsdam (Germany); and others

    2013-02-01

    The near-infrared is an important part of the spectrum in astronomy, especially in cosmology because the light from objects in the early universe is redshifted to these wavelengths. However, deep near-infrared observations are extremely difficult to make from ground-based telescopes due to the bright background from the atmosphere. Nearly all of this background comes from the bright and narrow emission lines of atmospheric hydroxyl (OH) molecules. The atmospheric background cannot be easily removed from data because the brightness fluctuates unpredictably on short timescales. The sensitivity of ground-based optical astronomy far exceeds that of near-infrared astronomy because of this long-standing problem. GNOSIS is a prototype astrophotonic instrument that utilizes 'OH suppression fibers' consisting of fiber Bragg gratings and photonic lanterns to suppress the 103 brightest atmospheric emission doublets between 1.47 and 1.7 {mu}m. GNOSIS was commissioned at the 3.9 m Anglo-Australian Telescope with the IRIS2 spectrograph to demonstrate the potential of OH suppression fibers, but may be potentially used with any telescope and spectrograph combination. Unlike previous atmospheric suppression techniques GNOSIS suppresses the lines before dispersion and in a manner that depends purely on wavelength. We present the instrument design and report the results of laboratory and on-sky tests from commissioning. While these tests demonstrated high throughput ( Almost-Equal-To 60%) and excellent suppression of the skylines by the OH suppression fibers, surprisingly GNOSIS produced no significant reduction in the interline background and the sensitivity of GNOSIS+IRIS2 is about the same as IRIS2. It is unclear whether the lack of reduction in the interline background is due to physical sources or systematic errors as the observations are detector noise dominated. OH suppression fibers could potentially impact ground-based astronomy at the level of adaptive optics or

  1. GNOSIS: THE FIRST INSTRUMENT TO USE FIBER BRAGG GRATINGS FOR OH SUPPRESSION

    International Nuclear Information System (INIS)

    Trinh, Christopher Q.; Ellis, Simon C.; Bland-Hawthorn, Joss; Bryant, Julia; O'Byrne, John; Lawrence, Jon S.; Horton, Anthony J.; Shortridge, Keith; Case, Scott; Colless, Matthew; Gers, Luke; Lee, Steve; Miziarski, Stan; Leon-Saval, Sergio G.; Couch, Warrick; Glazebrook, Karl; Freeman, Kenneth; Löhmannsröben, Hans-Gerd; Haynes, Roger; Roth, Martin M.

    2013-01-01

    The near-infrared is an important part of the spectrum in astronomy, especially in cosmology because the light from objects in the early universe is redshifted to these wavelengths. However, deep near-infrared observations are extremely difficult to make from ground-based telescopes due to the bright background from the atmosphere. Nearly all of this background comes from the bright and narrow emission lines of atmospheric hydroxyl (OH) molecules. The atmospheric background cannot be easily removed from data because the brightness fluctuates unpredictably on short timescales. The sensitivity of ground-based optical astronomy far exceeds that of near-infrared astronomy because of this long-standing problem. GNOSIS is a prototype astrophotonic instrument that utilizes 'OH suppression fibers' consisting of fiber Bragg gratings and photonic lanterns to suppress the 103 brightest atmospheric emission doublets between 1.47 and 1.7 μm. GNOSIS was commissioned at the 3.9 m Anglo-Australian Telescope with the IRIS2 spectrograph to demonstrate the potential of OH suppression fibers, but may be potentially used with any telescope and spectrograph combination. Unlike previous atmospheric suppression techniques GNOSIS suppresses the lines before dispersion and in a manner that depends purely on wavelength. We present the instrument design and report the results of laboratory and on-sky tests from commissioning. While these tests demonstrated high throughput (≈60%) and excellent suppression of the skylines by the OH suppression fibers, surprisingly GNOSIS produced no significant reduction in the interline background and the sensitivity of GNOSIS+IRIS2 is about the same as IRIS2. It is unclear whether the lack of reduction in the interline background is due to physical sources or systematic errors as the observations are detector noise dominated. OH suppression fibers could potentially impact ground-based astronomy at the level of adaptive optics or greater. However, until a

  2. Semi-quantitative prediction of a multiple API solid dosage form with a combination of vibrational spectroscopy methods.

    Science.gov (United States)

    Hertrampf, A; Sousa, R M; Menezes, J C; Herdling, T

    2016-05-30

    Quality control (QC) in the pharmaceutical industry is a key activity in ensuring medicines have the required quality, safety and efficacy for their intended use. QC departments at pharmaceutical companies are responsible for all release testing of final products but also all incoming raw materials. Near-infrared spectroscopy (NIRS) and Raman spectroscopy are important techniques for fast and accurate identification and qualification of pharmaceutical samples. Tablets containing two different active pharmaceutical ingredients (API) [bisoprolol, hydrochlorothiazide] in different commercially available dosages were analysed using Raman- and NIR Spectroscopy. The goal was to define multivariate models based on each vibrational spectroscopy to discriminate between different dosages (identity) and predict their dosage (semi-quantitative). Furthermore the combination of spectroscopic techniques was investigated. Therefore, two different multiblock techniques based on PLS have been applied: multiblock PLS (MB-PLS) and sequential-orthogonalised PLS (SO-PLS). NIRS showed better results compared to Raman spectroscopy for both identification and quantitation. The multiblock techniques investigated showed that each spectroscopy contains information not present or captured with the other spectroscopic technique, thus demonstrating that there is a potential benefit in their combined use for both identification and quantitation purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. LC-MS/MS signal suppression effects in the analysis of pesticides in complex environmental matrices.

    Science.gov (United States)

    Choi, B K; Hercules, D M; Gusev, A I

    2001-02-01

    The application of LC separation and mobile phase additives in addressing LC-MS/MS matrix signal suppression effects for the analysis of pesticides in a complex environmental matrix was investigated. It was shown that signal suppression is most significant for analytes eluting early in the LC-MS analysis. Introduction of different buffers (e.g. ammonium formate, ammonium hydroxide, formic acid) into the LC mobile phase was effective in improving signal correlation between the matrix and standard samples. The signal improvement is dependent on buffer concentration as well as LC separation of the matrix components. The application of LC separation alone was not effective in addressing suppression effects when characterizing complex matrix samples. Overloading of the LC column by matrix components was found to significantly contribute to analyte-matrix co-elution and suppression of signal. This signal suppression effect can be efficiently compensated by 2D LC (LC-LC) separation techniques. The effectiveness of buffers and LC separation in improving signal correlation between standard and matrix samples is discussed.

  4. High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer.

    Science.gov (United States)

    Barash, Oleksii O; Hinckley, Mary D; Rosenbluth, Evan M; Ivani, Kristen A; Weckstein, Louis N

    2017-11-01

    Does high gonadotropin dosage affect euploidy and pregnancy rates in PGS cycles with single embryo transfer? High gonadotropin dosage does NOT affect euploidy and pregnancy rates in PGS cycles with single embryo transfer. PGS has been proven to be the most effective and reliable method for embryo selection in IVF cycles. Euploidy and blastulation rates decrease significantly with advancing maternal age. In order to recruit an adequate number of follicles, the average dosage of gonadotropins administered during controlled ovarian stimulation in IVF cycles often increases significantly with advancing maternal age. A retrospective study of SNP (Single Nucleotide Polymorphism) PGS outcome data from blastocysts biopsied on day 5 or day 6 was conducted to identify differences in euploidy and clinical pregnancy rates. Seven hundred and ninety four cycles of IVF treatment with PGS between January 2013 and January 2017 followed by 651 frozen embryo transfers were included in the study (506 patients, maternal age (y.o.) - 37.2 ± 4.31). A total of 4034 embryos were analyzed (5.1 ± 3.76 per case) for euploidy status. All embryos were vitrified after biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. All cycles were analyzed by total gonadotropin dosage (5000 IU), by number of eggs retrieved (1-5, 5-10, 10-15 and >15 eggs) and patient's age (cycles) euploidy rates ranged from 62.3% (cycle) to 67.5% (>5000 IU were used in the IVF cycle) (OR = 0.862, 95% CI 0.687-1.082, P = 0.2) and from 69.5% (1-5 eggs retrieved) to 60.0% (>15 eggs retrieved) (OR = 0.658, 95% CI 0.405-1.071, P = 0.09). Similar data were obtained in the oldest group of patients (≥41 y.o. - 189 IVF cycles): euploidy rates ranged from 30.7 to 26.4% (OR = 0.811, 95% CI 0.452-1.454, P = 0.481) when analyzed by total dosage of gonadotropins used in the IVF cycle and from 40.0 to 30.7% (OR = 0.531, 95% CI 0.204-1.384, P = 0.19), when assessed by the total

  5. Thyroid suppression test with dextrothyroxine

    International Nuclear Information System (INIS)

    Rosenthal, D.; Fridman, J.; Ribeiro, H.B.

    1978-01-01

    The classic thyroid suppression test with triiodothyronine (l-T 3 ) has been shown to be efficient as an auxiliary method in the diagnosis of thyroid diseases, but should not be performed on elderly patients or on those with heart disease or a tendency to tachycardia. Since these subjects seem able to support a short period of dextro-thyronine (d-T 4 ) feeding, we compared the effect of d-T 4 and l-T 3 on the 24 hours thyroid uptake in euthyroid and hyperthyroid subjects. After basal radio-iodine uptake determination, 99 patients without hyperthyroidism and 27 with Graves' disease were randomly divided in 2 groups; one received 100μg of l-T 3 per day and the other 4 mg of d-T 4 per day, both groups being treated for a period of 10 days. At the end of this suppression period the 24 hours radio-iodine uptake was measured again and the percentual suppression index (S.I.) calculated. Since the comparison of the two groups showed no difference between the suppressive effect of l-T 3 and d-T 4 in euthyroid subjects, while dextro-thyronine, as levo-triiodothyronine, did not suppress the 24 hours uptake of hyperthyroid patients, l-T 3 or d-T 4 can be used interchangeably to test thyroid suppressibility. In the euthyroid subjects the normal range for the post-suppression uptake was 0-17.1% and for the suppression index 54,7.100% [pt

  6. Absorptive lasing mode suppression in ZnO nano- and microcavities

    Energy Technology Data Exchange (ETDEWEB)

    Wille, M.; Michalsky, T.; Krüger, E.; Grundmann, M.; Schmidt-Grund, R. [Universität Leipzig, Institut für Experimentelle Physik II, Linnéstraße 5, 04103 Leipzig (Germany)

    2016-08-08

    We conclusively explain the different lasing mode energies in ZnO nano- and microcavities observed by us and reported in literature. The limited penetration depth of usually used excitation lasers results in an inhomogeneous spatial gain region depending on the structure size and geometry. Hence, weakly or even nonexcited areas remain present after excitation, where modes are instantaneously suppressed by excitonic absorption. We compare the effects for ZnO microwires, nanowires, and tetrapod-like structures at room temperature and demonstrate that the corresponding mode selective effect is most pronounced for whispering-gallery modes in microwires with a hexagonal cross section. Furthermore, the absorptive lasing mode suppression will be demonstrated by correlating the spot size of the excitation laser and the lasing mode characteristic of a single ZnO nanowire.

  7. Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1 in development: implications for the evolution of imprinting.

    Directory of Open Access Journals (Sweden)

    Simao Teixeira da Rocha

    2009-02-01

    Full Text Available Genomic imprinting is a normal process that causes genes to be expressed according to parental origin. The selective advantage conferred by imprinting is not understood but is hypothesised to act on dosage-critical genes. Here, we report a unique model in which the consequences of a single, double, and triple dosage of the imprinted Dlk1/Pref1, normally repressed on the maternally inherited chromosome, can be assessed in the growing embryo. BAC-transgenic mice were generated that over-express Dlk1 from endogenous regulators at all sites of embryonic activity. Triple dosage causes lethality associated with major organ abnormalities. Embryos expressing a double dose of Dlk1, recapitulating loss of imprinting, are growth enhanced but fail to thrive in early life, despite the early growth advantage. Thus, any benefit conferred by increased embryonic size is offset by postnatal lethality. We propose a negative correlation between gene dosage and survival that fixes an upper limit on growth promotion by Dlk1, and we hypothesize that trade-off between growth and lethality might have driven imprinting at this locus.

  8. Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So-Yeon; Kim, Sun Ki [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Jee, Won-Hee [Catholic University of Korea, Department of Radiology, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of); Catholic University of Korea, Diagnostic Radiology, Seoul St. Mary' s Hospital, School of Medicine, Seoul (Korea, Republic of); Kim, Jung-Man [Catholic University of Korea, Department of Orthopedic Surgery, Seoul St. Mary' s Hospital, Seoul (Korea, Republic of)

    2011-02-15

    To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using {kappa} coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with ({kappa} = 0.87) or without ({kappa} = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

  9. Proton density-weighted MR imaging of the knee: fat suppression versus without fat suppression

    International Nuclear Information System (INIS)

    Lee, So-Yeon; Kim, Sun Ki; Jee, Won-Hee; Kim, Jung-Man

    2011-01-01

    To prospectively evaluate the diagnostic accuracy of proton density-weighted imaging with and without fat suppression for detecting meniscal tears. The study involved 48 patients who underwent arthroscopy less than 3 months after proton density-weighted imaging with and without fat suppression. Sagittal images were independently reviewed by two radiologists for the presence of meniscal tears. Medial and lateral menisci were separately analyzed in terms of anterior horn, body, and posterior horn. Interobserver agreement was assessed using κ coefficients. The McNemar test was used to determine any differences between the two methods in terms of sensitivity and specificity. Arthroscopy findings were used as the diagnostic reference standard. Arthroscopy revealed 71 tears involving 85 meniscal segments: 34 medial meniscal segments and 51 lateral meniscal segments. The sensitivity, specificity, and accuracy of each radiologist were 95% (81/85), 92% (186/203), and 93% (267/288), and 93% (79/85), 93% (189/203), and 93% (268/288) when using fat-suppressed proton density-weighted imaging, and 91% (77/85), 93% (189/203), and 92% (266/288), and 91% (77/85), 93% (188/203), and 92% (265/288) when using proton density-weighted imaging without fat suppression, respectively. Interobserver agreement for meniscal tears was very high with proton-weighted imaging with (κ = 0.87) or without (κ = 0.86) fat suppression. There were no significant differences for detection of medial meniscal tears when using proton density-weighted imaging with or without fat suppression for both readers (p > 0.05). Fat-suppressed proton density-weighted imaging can replace proton density-weighted imaging without fat suppression for the detection of meniscal tears. (orig.)

  10. Frequency-dependent Alfvén-wave Propagation in the Solar Wind: Onset and Suppression of Parametric Decay Instability

    Science.gov (United States)

    Shoda, Munehito; Yokoyama, Takaaki; Suzuki, Takeru K.

    2018-06-01

    Using numerical simulations we investigate the onset and suppression of parametric decay instability (PDI) in the solar wind, focusing on the suppression effect by the wind acceleration and expansion. Wave propagation and dissipation from the coronal base to 1 au is solved numerically in a self-consistent manner; we take into account the feedback of wave energy and pressure in the background. Monochromatic waves with various injection frequencies, f 0, are injected to discuss the suppression of PDI, while broadband waves are applied to compare the numerical results with observation. We find that high-frequency ({f}0≳ {10}-3 {Hz}) Alfvén waves are subject to PDI. Meanwhile, the maximum growth rate of the PDI of low-frequency ({f}0≲ {10}-4 {Hz}) Alfvén waves becomes negative due to acceleration and expansion effects. Medium-frequency ({f}0≈ {10}-3.5 {Hz}) Alfvén waves have a positive growth rate but do not show the signature of PDI up to 1 au because the growth rate is too small. The medium-frequency waves experience neither PDI nor reflection so they propagate through the solar wind most efficiently. The solar wind is shown to possess a frequency-filtering mechanism with respect to Alfvén waves. The simulations with broadband waves indicate that the observed trend of the density fluctuation is well explained by the evolution of PDI while the observed cross-helicity evolution is in agreement with low-frequency wave propagation.

  11. Bone-suppressed radiography using machine learning

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun Beom; Kim, Dae Cheon; Kim, Ho Kyung [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    The single-shot dual-energy imaging suffers from reduced contrast-to-noise ratio performance due to poor spectral separation. Tomosynthesis requires more complex motion equipment and may require higher patient dose. An alternative tissue-specific imaging technique was introduced. This alternative technique usually possesses a filter to generate bone-only images for given digital radiographs. Therefore, it provides soft-tissue-enhanced images from the subtraction of given radiographs and filtered bone-only images. Only bone-suppressed imaging capability is a limitation of the method. The filter can be obtained from a machine-learning algorithm, e.g. artificial neural network (ANN), with the dual-energy bone-only images (called 'teaching' images). We suspect the robustness of the filter may be dependent upon the number of teaching images and the number of patients from whose radiographs we obtain the teaching images. In this study, we design an ANN to obtain a bone-extracting filter from a radiograph, and investigate the filter properties with respect to various ANN parameters. Preliminary results are summarized in Fig. 3. We extracted 5,000 subregions in a 21x21 pixel format from the lung region in the bone-enhanced dual-energy image and we used them for teaching images during training the ANN. The resultant bone-enhanced image from the ANN nonlinear filter is shown in Fig. 3 (a). From the weighted logarithmic subtraction between Fig. 2 (a) and Fig. 3 (a), we could obtain the bone-suppressed image as shown in Fig. 3 (b). The quality of the bone-suppressed image is comparable to the ground truth Fig. 2 (c).

  12. Bone-suppressed radiography using machine learning

    International Nuclear Information System (INIS)

    Park, Jun Beom; Kim, Dae Cheon; Kim, Ho Kyung

    2016-01-01

    The single-shot dual-energy imaging suffers from reduced contrast-to-noise ratio performance due to poor spectral separation. Tomosynthesis requires more complex motion equipment and may require higher patient dose. An alternative tissue-specific imaging technique was introduced. This alternative technique usually possesses a filter to generate bone-only images for given digital radiographs. Therefore, it provides soft-tissue-enhanced images from the subtraction of given radiographs and filtered bone-only images. Only bone-suppressed imaging capability is a limitation of the method. The filter can be obtained from a machine-learning algorithm, e.g. artificial neural network (ANN), with the dual-energy bone-only images (called 'teaching' images). We suspect the robustness of the filter may be dependent upon the number of teaching images and the number of patients from whose radiographs we obtain the teaching images. In this study, we design an ANN to obtain a bone-extracting filter from a radiograph, and investigate the filter properties with respect to various ANN parameters. Preliminary results are summarized in Fig. 3. We extracted 5,000 subregions in a 21x21 pixel format from the lung region in the bone-enhanced dual-energy image and we used them for teaching images during training the ANN. The resultant bone-enhanced image from the ANN nonlinear filter is shown in Fig. 3 (a). From the weighted logarithmic subtraction between Fig. 2 (a) and Fig. 3 (a), we could obtain the bone-suppressed image as shown in Fig. 3 (b). The quality of the bone-suppressed image is comparable to the ground truth Fig. 2 (c).

  13. Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression

    International Nuclear Information System (INIS)

    Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X.; Walterscheid, Jeffrey P.; Ullrich, Stephen E.

    2004-01-01

    Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependant manner. The release of biological response modifiers, particularly prostaglandin E 2 (PGE 2 ), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE 2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE 2 secretion. Jet fuel-induced PGE 2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin

  14. 75 FR 26647 - Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution

    Science.gov (United States)

    2010-05-12

    .... FDA-2010-N-0002] Ophthalmic and Topical Dosage Form New Animal Drugs; Ivermectin Topical Solution... are treated with a topical solution of ivermectin. DATES: This rule is effective May 12, 2010. FOR... ANADA 200-340 for PRIVERMECTIN (ivermectin), a topical solution used on cattle to control infestations...

  15. Phosphatidylinositol response and proliferation of oxidative enzyme-activated human T lymphocytes: suppression by plasma lipoproteins

    International Nuclear Information System (INIS)

    Akeson, A.L.; Scupham, D.W.; Harmony, J.A.

    1984-01-01

    The phosphatidylinositol (PI) response and DNA synthesis of neuraminidase and galactose oxidase (NAGO)-stimulated human T lymphocytes are suppressed by low density lipoproteins (LDL). To understand the mechanism of lymphocyte activation more fully, the PI response and DNA synthesis and suppression of these events by LDL in NAGO-stimulated T lymphocytes were characterized. Between 30 min and 6 hr after NAGO stimulation, there was an increase of 32 Pi incorporation into PI without increased incorporation into the phosphorylated forms of PI or into other phospholipids. DNA synthesis as determined by [ 3 H]thymidine incorporation depended on the lymphocyte-accessory monocyte ratio and total cell density. Optimal stimulation of the PI response and DNA synthesis occurred at the same concentration of neuraminidase and galactose oxidase. While the PI response was only partially suppressed by LDL with optimal suppression at 10 to 20 micrograms of protein/ml, DNA synthesis was completely suppressed although at much higher LDL concentrations, greater than 100 micrograms protein/ml. As monocyte numbers are increased, LDL suppression of DNA synthesis is decreased. The ability of NAGO to stimulate the PI response and DNA synthesis in a similar way, and the suppression of both events by LDL, suggests the PI response is important for lymphocyte activation and proliferation. Stimulation of human T lymphocytes by oxidative mitogens, neuraminidase, and galactose oxidase caused increased phosphatidylinositol metabolism and increased DNA synthesis. Both responses were suppressed by low density lipoproteins

  16. The effect of two dosage of BCAA supplementation on wrestlers’ serum indexes on cellular injury

    Directory of Open Access Journals (Sweden)

    Ramin Amirsasan

    2012-01-01

    Full Text Available Background: A few studies were done to examine the effect of different dosage of branched-chain amino acid (BCAA supplementation on serum indexes of muscle injury in wrestlers. The purpose of this research was to compare the effects of two dosage of branched-chain amino acid supplementation on muscle serumic damage indexes after heavy resistance exercise in wrestlers.Materials and Method: Twenty-nine young wrestlers were randomly selected and divided into three groups. All subjects were participated in heavy resistance exercise (3 sets, 10 repetitions, 80% 1RM. The BCAA was given at doses of 210 and 450 mg/kg for supplemental groups 1 and 2 respectively, 30 minutes before and after to exercise test and dextrin was given at dose of 210 mg/kg for control group. To identify enzymes activity (IU/L, venous blood samples were obtained 30 min prior to exercise and at 24 and 48 hrs after exercise. Data were statistically analyzed using ANOVA with repeated measures and Bonfferoni post hoc test (p≥ 0.05.Results: Based on this study results, CPK, LDH, CPKMB activity were significantly increased (p<0.05 in all groups. CPK, LDH, CPKMB indexes having the highest activity in the control group, but there were no significant differences between all groups. Conclusion: These results provide evidence that the use of two different dosage of BCAA could not decrease muscle damage associated with heavy resistance exercise

  17. Formulation and process considerations affecting the stability of solid dosage forms formulated with methacrylate copolymers.

    Science.gov (United States)

    Petereit, H U; Weisbrod, W

    1999-01-01

    General considerations concerning the stability of coated dosage forms are discussed, in order to avoid predictable interactions which may cause long-term stability problems. As polymers themselves maintain a high chemical stability and a low reactivity, instability phenomena mainly have to be explained by interactions of low molecular weight substances or physical changes. Possible interactions of functional groups can be predicted easily and insulating subcoates are proper countermeasures. Impurities, remaining in the polymeric material from the manufacturing process, may accelerate the hydrolysis of sensitive drugs. Instabilities of coated dosage forms are mainly based on physical interactions, caused by improper formulations of coating suspensions (i.e. plasticizers or pigments) or the film coating process. Residual moisture or solvents, probably enclosed in the core and migrating over time, may increase the permeability of coatings, due to plasticizing effects. The functionality of coatings from aqueous dispersions is linked to coalescence of latex particles. Thus any incomplete film formation, caused by too high or too low coating temperatures, may result in high permeable coatings. During storage, preferably under stress conditions this process will continue and thus change the release profile. Therefore bed temperatures of 10-20 degrees C above MFT must ensure the formation of homogeneous polymer layers during the coating process. Stability test procedures and packaging materials also need to be adapted to the physicochemical properties of the dosage form, in order to get meaningful results in stability tests.

  18. Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes

    International Nuclear Information System (INIS)

    Chen, Yanyan; Xue, Peng; Hou, Yongyong; Zhang, Hao; Zheng, Hongzhi; Zhou, Tong; Qu, Weidong; Teng, Weiping; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2013-01-01

    Transcriptional signaling through the antioxidant response element (ARE), orchestrated by the Nuclear factor E2-related factor 2 (Nrf2), is a major cellular defense mechanism against oxidative or electrophilic stress. Here, we reported that isoniazid (INH), a widely used antitubercular drug, displays a substantial inhibitory property against ARE activities in diverse mouse and human cells. In 3T3-L1 preadipocytes, INH concentration-dependently suppressed the ARE-luciferase reporter activity and mRNA expression of various ARE-dependent antioxidant genes under basal and oxidative stressed conditions. In keeping with our previous findings that Nrf2-ARE plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein β (C/EBPβ) and peroxisome proliferator-activated receptor γ (PPARγ), suppression of ARE signaling by INH hampered adipogenic differentiation of 3T3-L1 cells and human adipose-derived stem cells (ADSCs). Following adipogenesis induced by hormonal cocktails, INH-treated 3T3-L1 cells and ADSCs displayed significantly reduced levels of lipid accumulation and attenuated expression of C/EBPα and PPARγ. Time-course studies in 3T3-L1 cells revealed that inhibition of adipogenesis by INH occurred in the early stage of terminal adipogenic differentiation, where reduced expression of C/EBPβ and C/EBPδ was observed. To our knowledge, the present study is the first to demonstrate that INH suppresses ARE signaling and interrupts with the transcriptional network of adipogenesis, leading to impaired adipogenic differentiation. The inhibition of ARE signaling may be a potential underlying mechanism by which INH attenuates cellular antioxidant response contributing to various complications. - Highlights: • Isoniazid suppresses ARE-mediated transcriptional activity. • Isoniazid inhibits adipogenesis in preadipocytes. • Isoniazid suppresses adipogenic gene expression during adipogenesis

  19. Prostaglandin E1 treatment in ductus dependent congenital cardiac malformation. A review of the treatment of 34 neonates

    DEFF Research Database (Denmark)

    Høst, A; Halken, S; Kamper, J

    1988-01-01

    and safe regiment that could be initiated after clinical diagnosis of a severe duct dependent cardiac defect, whose clinical course would be adversely affected by ductus closure. After an initial dosage of 0.1 micrograms/kg/min, effective clinical improvement was achieved in 28 infants (82%). In all 28...

  20. Thermal stratification in a scaled-down suppression pool of the Fukushima Daiichi nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Byeongnam, E-mail: jo@vis.t.u-tokyo.ac.jp [Nuclear Professional School, The University of Tokyo, 2-22 Shirakata, Tokai-mura, Ibaraki 319-1188 (Japan); Erkan, Nejdet [Nuclear Professional School, The University of Tokyo, 2-22 Shirakata, Tokai-mura, Ibaraki 319-1188 (Japan); Takahashi, Shinji [Department of Nuclear Engineering and Management, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Song, Daehun [Nuclear Professional School, The University of Tokyo, 2-22 Shirakata, Tokai-mura, Ibaraki 319-1188 (Japan); Hyundai and Kia Corporate R& D Division, Hyundai Motors, 772-1, Jangduk-dong, Hwaseong-Si, Gyeonggi-Do 445-706 (Korea, Republic of); Sagawa, Wataru; Okamoto, Koji [Nuclear Professional School, The University of Tokyo, 2-22 Shirakata, Tokai-mura, Ibaraki 319-1188 (Japan)

    2016-08-15

    Highlights: • Thermal stratification was reproduced in a scaled-down suppression pool of the Fukushima Daiichi nuclear power plants. • Horizontal temperature profiles were uniform in the toroidal suppression pool. • Subcooling-steam flow rate map of thermal stratification was obtained. • Steam bubble-induced flow model in suppression pool was suggested. • Bubble frequency strongly depends on the steam flow rate. - Abstract: Thermal stratification in the suppression pool of the Fukushima Daiichi nuclear power plants was experimentally investigated in sub-atmospheric pressure conditions using a 1/20 scale torus shaped setup. The thermal stratification was reproduced in the scaled-down suppression pool and the effect of the steam flow rate on different thermal stratification behaviors was examined for a wide range of steam flow rates. A sparger-type steam injection pipe that emulated Fukushima Daiichi Unit 3 (F1U3) was used. The steam was injected horizontally through 132 holes. The development (formation and disappearance) of thermal stratification was significantly affected by the steam flow rate. Interestingly, the thermal stratification in the suppression pool vanished when subcooling became lower than approximately 5 °C. This occurred because steam bubbles are not well condensed at low subcooling temperatures; therefore, those bubbles generate significant upward momentum, leading to mixing of the water in the suppression pool.